ANS: Receptor Function

What are examples of G-protein coupled receptors?

Cholinergic-receptor type: Muscarinic (1-5) Adrenergic-receptor type: alpha, beta, and dopamine.

Receptors that produce smooth muscle contraction (M3 or alpha1) are couple to what G-protein?

Gq

Will the effects of a muscarinic-receptor agonist always decrease heart rate when it is administered systemically.

No, There are muscarinic-receptors on the vasculature (even though there are no cholinergic-nerves innervating) that can be activated if by drugs administered IV, etc. When this happens nitric oxide is released producing vasodilation. Vasodilation will produce compensatory baroreceptor responses resulting in increased sympathetic flow to heart and a subsequent increase in heart rate. Note: this compensatory response can be blocked by ganglionic blockers or muscarinic antagonist.

Nicotinic cholinergic receptors locations

Somatic NS: Neuromuscular junction ANS: Ganglionic Junctions (parasympathetic and sympathetic), Adrenal Medulla CNS

Which autonomic receptor subtype is primarily responsible for mediating the vasodilation seen in certain vascular beds, such as those in skeletal muscles? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Beta-2 adrenergic receptors D) Muscarinic cholinergic receptors

The correct answer is C) Beta-2 adrenergic receptors. These receptors are predominantly located in skeletal muscle vasculature. Stimulation of beta-2 receptors by sympathetic nerves leads to vasodilation and increased blood flow to skeletal muscles.

Activation of which autonomic receptor leads to bronchial smooth muscle relaxation and dilation of the airways? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Beta-2 adrenergic receptors D) Muscarinic cholinergic receptors

The correct answer is C) Beta-2 adrenergic receptors. These receptors are primarily located in bronchial smooth muscle. Activation of beta-2 receptors by sympathetic stimulation leads to relaxation of bronchial smooth muscle, resulting in bronchodilation and increased airflow.

Which type of autonomic receptor is responsible for the pupillary constriction response seen in bright light conditions? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Beta-2 adrenergic receptors D) Muscarinic cholinergic receptors

The correct answer is D) Muscarinic cholinergic receptors. These receptors are responsible for pupillary constriction (miosis) in response to parasympathetic stimulation. Activation of muscarinic receptors by acetylcholine causes the circular muscles of the iris to contract, reducing pupil size and preventing excessive light from entering the eye.

What may happen when GPCR receptors are continually exposed to receptor agonist?

initially receptors may be uncoupled from the g-protein cascades (desensitization), this event can be followed by internalization of receptors into intracellular compartments where they can either be recycled back to the cell surface or destroyed in lysosomal compartments (down regulation)

What is the most common receptor type activated on organs when post-ganglionic parasympathetic neurons release their respective neurotransmitter?

muscarinic-cholinergic receptors, either M2 (heart) or M3 (smooth muscle and secretory glands)

What is enzyme is required for smooth muscle contraction (Note: not required in cardiac or skeletal muscle) and is inhibited when phosphorylated by PKA?

myosin light chain kinase

Increases in intracellular cAMP lead to activation of what kinase?

protein kinase A

Beta 2 adrenoceptors located on smooth muscle cells produce what?

smooth muscle relaxation

How does norepinephrine regulate its own synaptic release?

via alpha-2 presynaptic adrenoceptors. When norepinephrine is released it can 1) bind to post-synaptic receptors 2) be taken back up into presynaptic neuron 3) bind to presynaptic alpha-2 receptors. Alpha-2 receptor activation leads to a decrease in norepinehrine release.

Can a drug with no direct effects on the heart that produces vasodilation increase heart rate?

yes, via the baroreceptor compensatory response. The drop in blood pressure will result in sensory input to the brain and a CNS output to the body that involves an increase in sympathetic activity resulting in more norepinephrine released onto the heart and more activation of beta-1 receptors.

Epinephrine is a neurotransmitter and drug that activates all types of sympathetic receptors (alpha 1,2 and beta 1,2). When this drug is administered what will happen to the heart rate?

activation of beta-1 receptors should accelerate heart rate

Epinephrine is a neurotransmitter and drug that activates all types of sympathetic receptors (alpha 1,2 and beta 1,2). When this drug is administered what will happen to the lungs?

activation of beta-2 receptors on the lung should produce smooth muscle relaxation (bronchodilation)

Activation of the intracellular protein, Gs, leads to the activation of what effector protein?

adenylyl cyclase (converts ATP into the messenger cAMP)

Which neurotransmitter is released by both sympathetic and parasympathetic pre-ganglionic neurons.

acetylcholine

Which neurotransmitter stimulates all type of secretory events (salivation, lacrimation, sweating, gut, and lung)?

acetylcholine

The two main neurotransmitters used by the autonomic nervous system are

acetylcholine norepinephrine

Epinephrine is a neurotransmitter and drug that activates all types of sympathetic receptors (alpha 1,2 and beta 1,2). When this drug is administered in the presence of beta- adrenergic receptor antagonist what will happen to diastolic blood pressure ?

--it should go up. Blocking beta 2 receptors should produce unopposed alpha-1 receptor activation resulting in vasoconstriction and an increase in diastolic BP.

Parasympathetic post-ganglionic neurons innervate what organs.

1 Cranial roots: a. Vagus (X) =lung, heart, stomach, pancreas, small intestine. b. IX and VII tear and salivary glands c. III eye 2 Sacral roots: a. Large intestine b. Rectum c. Bladder d. Reproductive organs.

Which of the following type of drugs is most likely to produce all of the following symptoms: 1. Skeletal muscle contraction 2. Increase in vascular resistance and blood pressure 3. Increased lacrimation 4. Miosis (decreased iris diameter) 5. Urinary bladder sphincter relaxation A. A drug that activates nicotinic-cholinergic receptors B. A drug that activates alpha-1 adrenergic receptors C. A drug that activates M3-cholinergic receptors D. A drug that activates M2-cholinergic receptors E. A drug that block nicotinic receptors at autonomic ganglia

A. A drug that activates nicotinic-cholinergic receptors All neurons exiting the spinal chord synthesize and release acetylcholine (cholinergic neurons). The main post-synaptic receptor adjacent to the neurons exiting the spinal chord are nicotinic. This includes parasympathetic and sympathetic ganglionic junctions, the junction between sympathetic and the adrenal medulla, as well as on skeletal muscle. Also, when both parasympathetic and sympathetic neurons are co-activated the net response on co-innervated organs is parasympathetic.

Which of the following is correctly matched? Drug type Response to drug A. Beta 1-receptor agonist increase renin release from kidney B. Alpha 1-receptor agonist decrease in systolic blood pressure C. Beta-2 receptor agonist increase in diastolic blood pressure D. Muscarinic agonist pupillary dilation (mydriasis) E. Nicotinic agonist decrease blood pressure

A. Beta 1-receptor agonist increase renin release from kidney

Acetylcholine causes smooth muscle contraction A. By activating intracellular cascades involving the production of IP3 B. By decreasing potassium conductance C. By decreasing both nicotinic and muscarinic receptor activity D. By increasing activation of protein kinase A E. By stimulating production of intracellular cAMP

A. By activating intracellular cascades involving the production of IP3

Which statement is true regarding the autonomic nervous system (ANS)? A. Parasympathetic ANS when activated causes the bronchi to constrict B. Post ganglionic neuronal acetylcholine (ACH) release is an important regulator of vascular tone C. Norepinephrine regulates both parasympathetic and sympathetic ANS D. Sympathetic ANS when activated decreases GI sphincter tone E. Sympathetic ANS only uses norepinephrine to alter organ function

A. Parasympathetic ANS when activated causes the bronchi to constrict

In an experimental animal model the vagal nerve is stimulated and the membrane potential is measured in a cardiac SA nodal cell (before and after stimulation of the vagal nerve). Which of the following would most likely occur? A. Vagal nerve stimulation leads to the activation of the intracellular g-protein, Gi, in post-synaptic cells B. Vagal nerve stimulation leads to the activation of M3 receptors on cardiac cells C. Vagal nerve stimulation leads to the increase in intracellular calcium, in post-synaptic cells D. Vagal nerve release of norepinephrine results in hyperpolarizes of cardiac myocytes E. Vagal nerve stimulation leads increased opening of voltage gated sodium channels in cardiac myocytes

A. Vagal nerve stimulation leads to the activation of the intracellular g-protein, Gi, in post-synaptic cells.

Norepinephrine bound to receptors on the smooth muscle cells causes smooth muscle contraction via which signalling cascade listed below? A. alpha1-R stimulation activates Gq which in turn causes PLC to release [IP3] and the intracellular release of [Ca++] B. alpha 2-R stimulation activates Gs which in turn results in cAMP production and PKA activation C. Activation of Nicotinic R produces Ca++ mediated contraction D. beta 1-R stimulation activates Gs which in turn increases cAMP production, PKA activation and the subsequent increase in opening of voltage gated calcium channels E. Beta 2-R stimulation activates Gs, intracellular cAMP production and PKA phosphorylation of MLCK to increase its activity

A. alpha1-R stimulation activates Gq which in turn causes PLC to release [IP3] and the intracellular release of [Ca++]

Which of the following is drug when provided to an animal model will produce an increase in HR when given alone but when given after administration of a ganglion blocker (cholinergic-nicotinic-receptor antagonist) will produce a decrease in HR? Acetylcholine Norepinephrine Vasoconstrictor agent Beta Agonist Muscarinic antagonist

Acetylcholine Drugs can increase the heart rate DIRECTLY by activating beta-1-adrenergic receptors located on heart-cells and or by producing vasodilation which in turn will cause the autonomic reflex via the barro stretch receptors to activate a neural increase in sympathetic pre-ganglionic that activate post ganglionic neurons that in turn release norepinephrine the endogenous activator of beta-1 receptors (see diagram for reflex schematic). In this case acetylcholine induces vasodilation that stimulates the INDIRECT sympathetic response which out competes the direct response on the heart. The ganglion blocker prevents sympathetic response so all that is left is the direct acetylcholine-induced decreases in HR.

What receptor subtype is responsible for norepinephrine-induced smooth muscle contraction?

Alpha-1-adrenergic receptors.

Norepinephrine released by sympathetic ANS neurons A. Activates both muscarinic and nicotinic receptors B. Decreases its own release from presynaptic SANS neurons C. Decreases thermoregulatory sweat production D. Reduces GI sphincter contraction E. Reduces liver glucose production

B. Decreases its own release from presynaptic SANS neurons

A 53-year-old male patient is having problems keeping his eyes open due to his condition of myasthenia gravis. He is treated with a drug that prevents the breakdown of acetylcholine (released by neurons). The use of this drug results in increased synaptic acetylcholine levels at peripheral-cholinergic-nerve-junctions. What is the most likely physiologic response to this type of drug? A. Inhibition of epinephrine release from adrenal medulla B. Increased gastrointestinal peristalsis, diarrhea, and flatulence C. Hyperpolarization of post-ganglionic neurons D. Relaxation of bronchiolar smooth muscle (bronchodilation) E. Skeletal muscle relaxation

B. Increased gastrointestinal peristalsis, diarrhea, and flatulence Drugs that increase acetylcholine at synaptic junctions by preventing breakdown will affect both parasympathetic and sympathetic autonomic ganglia. In addition, on organs that are innervated by cholinergic neurons (adrenal medulla, sweat glands, and skeletal muscle) will also be activated. Think of the mneumonic DUMBBELS Diarhea (muscarinic activation of parastalis and sphincter relaxation) Urination (muscarinic activation of bladder wall contraction and sphincter relaxation. Miosis (pin point pupils caused by muscarinic activation of circular constrictor muscles of eye) Bronchoconstriction (M3 on lungs) Bradycardia (M2 on heart) Excitation of skeletal muscles (nicotinic on Skeletal muscle) Lacrimation Sweating Salivation all M3 activated The predominate effect when both sympathetic and parasympathetic ganglion are co stimulated is a parasympathetic effect, except on the vasculature, which is not innervated by the parasympathetic nervous system.

A 53-year-old male patient with stable angina is treated with nitroglycerin. A drug that breaks down into nitric oxide resulting in vasodilation. Which compensatory response listed below may follow a drop in blood pressure? A. Increased activation of myosin-light-chain kinase in cardiac myocytes B. Increased production of cAMP in cardiac myocytes C. Increased stimulation of M2-cholinergic receptors D. Increased release of acetylcholine on cardiac myocytes E. Increased activation of parasympathetic (vagal neurons)

B. Increased production of cAMP in cardiac myocytes A drop in blood pressure will be detected by baro-receptors, activation of signals to the vasomoter centers of the CNS that will subsequently adjust ANS outflow. If a drop in blood pressure is measured the response will be to increase sympathetic activity resulting in NE release on cardiac pacemaker cells, subsequent beta-1 receptor activation, cAMP generation, PKA activation resulting in influx of sodium and calcium.

Which system when activated promotes digestion, urination, and defecation? A. Somatic nervous system B. Parasympathetic autonomic nervous system (PANS) C. Sympathetic autonomic nervous system (SANS) D. Both SANS and PANS E. All three systems listed above

B. Parasympathetic autonomic nervous system (PANS)

Which statement is true about the peripheral autonomic nervous system (ANS)? A. All sympathetic-postganglionic neurons are noradrenergic (synthesize and release NE) B. Postganglionic parasympathetic neurons are always cholinergic C. Postganglionic sympathetic neurons activate only adrenergic receptors (alpha and beta) D. Norepinephrine regulates both parasympathetic and sympathetic ANS E. Sympathetic ANS when activated increases bronchial smooth muscle tone (contraction)

B. Postganglionic parasympathetic neurons are always cholinergic

Which statement is true about the peripheral autonomic nervous system (ANS)? A. Norepinephrine regulates both parasympathetic and sympathetic ANS B. Pre-ganglionic ANS neurons synthesize and release acetylcholine C. Only parasympathetic ANS neurons exiting the spinal chord are cholinergic D. Postganglionic sympathetic neurons activate only adrenergic receptors (alpha and beta) E. Parasympathetic ANS increases thermoregulatory sweating via activation of muscarinic receptors

B. Pre-ganglionic ANS neurons synthesize and release acetylcholine All neurons exiting the spinal chord synthesize and release acetylcholine (cholinergic neurons). The main post-synaptic receptor adjacent to the neurons exiting the spinal chord are nicotinic. This includes parasympathetic and sympathetic ganglionic junctions, the junction between sympathetic and the adrenal medulla, as well as on skeletal muscle.

Which type of adrenergic receptors when activated are coupled to the G protein (G-alpha-S)?

Beta 1 and 2 adrenergic receptors

What type of adrenergic receptor is found on cardiac tissue?

Beta-one receptors are the principal adrenergic-receptor type located on the heart and beta-two are the principal type located on the lungs. A good mnemonic to keep beta 1 vs. beta 2 receptor location straight is; one heart and two lungs.

How does activation of M3 cholinergic receptors and alpha-1 adrenergic receptors produce smooth muscle contraction?

By increasing intracellular calcium. Both M3 and alpha-1 activated Gq, this in turn stimulates phospholipase C. When activated PLC cleaves the messenger sugar , IP3, off of the lipid PIP2. IP3 increases release of calcium from the sarcoplasmic reticulum (calcium storage organelle). Calmodulin bound to Ca++ stimulates MLCK which phosphorylates MLC allowing contraction.

Which of the following is correctly matched? Drug type Response to drug A. Alpha 1-receptor activation dec. in systolic blood pressure B. Beta-2 receptor activation inc. in diastolic blood pressure C. Alpha 2 -receptor activation dec, neuronal norepinephrine release D. Muscarinic agonist pupillary dilation (mydriasis) E. Nicotinic agonist dec. in blood pressure

C. Alpha 2 -receptor activation dec, neuronal norepinephrine release

During a routine fundus examination eye drops containing a drug to dilate the patients pupils is used. The patient is informed that a side effect of the drug is that they will not be able to focus on near objects. What receptor is this drug preventing from being activated? A. Alpha-1 adrenergic receptors B. Alpha-2 cholinergic receptors C. M3 cholinergic receptors D. Beta-1 adrenergic receptors E. Nicotinic cholinergic receptors

C. M3 cholinergic receptors There are two clinical ways to dilate the pupil: 1) An alpha-1 receptor agonist producing radial muscle contraction and 2) Muscarinic antagonist preventing circular constrictor muscle from contracting. M3 receptors control both the sphincter and ciliary muscles. The ciliary muscle are responsible for producing accommodation (ability to focus on near objects by rounding up the lens) when they contract. If the M3 receptor on the ciliary muscle is blocked the ciliary muscle is unable to move towards the lens allowing it to round up.

A 53-year-old man with hypertension is treated with, clonidine, a drug that stimulates alpha-2 adrenergic receptors. When this drug is used continually what would be the expected types of cellular adaptations? A. Downregulation of intracellular adenylyl cyclase B. Downregulation of peripheral beta-1 adrenergic receptors C. Upregulation of the number of post-synaptic alpha-1 adrenergic receptors D. Upregulation of the number of alpha-2 adrenergic receptors E. Upregulation of the g-protein, Gi

C. Upregulation of the number of post-synaptic alpha-1 adrenergic receptors Expect compensation to occur to the chronic presence of agonist. In the case of chronic exposure of clonidine, a alpha-2 selective agonist, the compensation would be to downregulate alpha-2 receptors in the presynaptic neuron where these receptors are located. The response to continual activation of alpha-2 receptors would result in a decrease in NE release. The post-synaptic membrane will respond to the absence of NE by upregulating alpha-1 receptors on blood vessels and beta-1 receptors on cardiac cells.

What are the three types of post ganglionic sympathetic efferent neurons?

Cholinergic (neurons that make and release acetylcholine) Noradgrenergic (neurons that make and release norepinephrine) Dopaminergic (neurons that make and release dopamine)

Which of the following drug type will produce all of the following symptoms when administered IV to a patient? Direct and indirect autonomic reflex effects are included. 1. Bradycardia 2. GI sphincter contraction 3. Hypertension 4. Mydriasis (pupillary dilator muscle contraction) A. A drug that activates beta-1 adrenergic receptors B. A drug that activates nicotinic-cholinergic receptors at autonomic ganglia C. A drug that decreases synaptic release of norepinephrine D. A drug that activates alpha-1 adrenergic receptors E. A drug that decreases intracellular calcium levels

D. A drug that activates alpha-1 adrenergic receptors Bradycardia (via reflex baro-receptor response increasing parasympathetic outflow to heart in response to an increase in blood pressure) GI sphincter contraction (alpha-1 receptor activation of sm contraction) Hypertension (alpha-1 receptor activation of sm contraction in blood vessels) Mydriasis (alpha-1 receptors on radial muscles of eye)

Miosis (decrease in pupillary diameter), bronchoconstriction, GI sphincter contraction and accommodation (adjusting for near vision) are mediated by: A. Activation of intracellular g-protein (Gs) B. Activation of alpha-1 adrenoceptor C. Activation of intracellular adenylyl cyclase D. Activation of intracellular phospholipase C E. Activation of beta-2 receptors

D. Activation of intracellular phospholipase C both the sympathetic (via alpha-1-R) and parasympathetic (via M3) post-synaptic organ response to produce smooth muscle contraction is mediated by the PI turnover pathway.

Which cell type uses influx of calcium from voltage gated calcium channels located on the plasma membrane to be the primary initiator of muscle contraction A. Smooth muscle cells B. Endothelial cells C. Nonadrenergic-noncholinergic neurons D. Skeletal muscle cells E. Cardiac muscle cells

E. Cardiac muscle cells

In an experimental animal model the vagal nerve is stimulated and an increase in gastric secretion is measured. Drug X is added to this assay system and the secretory rate does not increase after electrical stimulation of the vagal nerve. Drug X should also produce which response listed below. A. Aqueous humor outflow via the canal of Schlemm B. Lacrimation C. Skeletal muscle contraction D. Urination E. Constipation

E. Constipation Parasympathetic neurons release acetylcholine which binds to muscarinic receptors on organs. The muscarinic response is to increase secretions and contraction of gut and bladder walls. This drug must be a muscarinic receptor antagonist that will result in constipation.

Which statement is true about the peripheral autonomic nervous system (ANS)? A. All peripheral organ effects following the activation of sympathetic post-ganglionic neurons are mediated by norepinephrine. B. Parasympathetic post-ganglionic neurons innervate the vasculature of most visceral organs. C. Nicotinic (cholinergic-type) receptors are not located on organ tissue. D. Norepinephrine regulates both parasympathetic and sympathetic ANS E. The principle receptor type located on the post-synaptic (organ side) of the post-ganglionic-parasympathetic neuron is a muscarinic (cholinergic-type) receptor.

E. The principle receptor type located on the post-synaptic (organ side) of the post-ganglionic-parasympathetic neuron is a muscarinic (cholinergic-type) receptor.

On what organ tissue is it functionally important for the parasympathetic nervous system to produce smooth muscle relaxation?

GU and GI sphincters

Epinephrine is a neurotransmitter and drug that activates all types of sympathetic receptors (alpha 1,2 and beta 1,2). When this drug is administered in the presence of an alpha-1 adrenergic receptor antagonist what will happen to diastolic blood pressure ?

It should go down. During diastole, alpha-1 (contraction) and beta-2 (relaxation) are responsible for blood pressure. Epinephrine effects on beta-2, with the alpha effects blocked, should produce relaxation and a drop in blood pressure.

Nicotinic cholinergic receptors function

Ligand gated cation channel, composed of 4 subunits that come together to form pore ion channels. Acetylcholine binding opens flow of cations into cell. The channel is a site for voltage gating, phosphorylation.

Which autonomic receptor, when activated, will decrease heart rate.

M2 cholinergic receptor: Acetylcholine-induced-muscarinic-receptor-activation liberates the beta-gamma subunit from the alpha subunit of Gi. The free beta-gamma subunit activates voltage-gated-potassium channels (GIRK 1 and 4) resulting in charged-ion outflow causing hyperpolarization (see figure). Potassium ion outflow lowers the resting potential and requires more cation influx during the action potential, which increases the time to reach action-potential-threshold. This results in a slower SA pacemaker activity.

What receptor is activated to produce salivation, lacrimation, and thermoregulatory sweating?

Muscarinic cholinergic receptors. Lacrimation and salivation are parasympathetic responses. Sweating is a sympathetic response.

Most common post-synaptic receptor located on post-junctional neurons or cells innervated by neurons exiting the spinal chord.

Nicotinic cholinergic receptor

Which type of autonomic receptor is a ion channel?

Nicotinic-cholinergic receptors. These receptors are ion channels formed when 5 transmembrane proteins associate together to form a pentameric-cation-selective pore. Subtypes depend on subunit composition. NM (neuromuscular) = a2bgd NN (ganglionic)= a2b2 or a3b3 Location

Which of the following is drug when provided to an animal model will produce a decrease in HR when given alone but when given after administration of a ganglion blocker (cholinergic-nicotinic-receptor antagonist) will produce an increase in HR? Acetylcholine Norepinephrine Vasoconstrictor agent Beta Agonist Muscarinic antagonist

Norepinephrine Drugs can decrease the heart rate directly by activating cholinergic (M2) receptors and or by producing vasoconstriction (alpha-adrenergic receptor activation) which in turn will cause the autonomic reflex via the barro stretch receptors to activate a neural increase in parasympathetic pre-ganglionic that activate post ganglionic neurons that in turn release acetylcholine the endogenous activator of M1 receptors. In this case norepinphrine activation of alpha-1 receptors leads to vasoconstriction and an increase in parasympathetic response that outcompetes its direct effect on the heart. In the presence of a ganglion blocker that parasympathetic response is blocked and all that is left is the activation of beta-1 receptors.

How does the parasympathetic nervous system produce smooth muscle relaxation?

P-ANS relaxation of GI and GU sphincters. This second, indirect, mechanism is produced when nitrous oxide (NO) is synthesized and released in response to muscrinic receptors activation on adjacent nerves or endothelial cells, depending on the organ. NO activates guanylyl cyclase and produces increases in intracellular cGMP. The cGMP cascades leads to opening of potassium channels producing an outflow of positive charge and the activation of a phosphatase that de phosphorylate ML-chain itself. Both events lead to relaxation.

Activation of alpha-2 adrenergic receptors on presynaptic terminals leads to inhibition of norepinephrine release. What is the primary effector molecule involved in this inhibitory effect? A) Adenylate cyclase B) Phospholipase C C) Guanylate cyclase D) G protein-coupled receptor kinase (GRK)

The correct answer is A) Adenylate cyclase. Activation of alpha-2 adrenergic receptors inhibits adenylate cyclase activity, leading to decreased cAMP levels. This in addition to increasing potassium outflow reduces the release of norepinephrine, exerting a negative feedback mechanism to regulate sympathetic neurotransmission.

Which of the following receptor subtypes utilizes the Gq protein pathway upon activation? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Beta-2 adrenergic receptors D) Nicotinic cholinergic receptors E) Alpha-2 adrenergic receptors

The correct answer is A) Alpha-1 adrenergic receptors. Activation of alpha-1 adrenergic receptors involves the Gq protein pathway, leading to the activation of phospholipase C (PLC) and production of inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers initiate various intracellular effects, including vasoconstriction.

Muscarinic cholinergic receptors in smooth muscle cells of the gastrointestinal tract activate phospholipase C upon stimulation. What is the ultimate effect of this activation on smooth muscle contraction? A) Contraction B) Relaxation C) Hyperpolarization D) No effect

The correct answer is A) Contraction. Activation of muscarinic cholinergic receptors in smooth muscle cells of the gastrointestinal tract involves the Gq protein pathway, leading to increased intracellular calcium and smooth muscle contraction.

Activation of beta-1 adrenergic receptors in cardiac myocytes increases contractility. What intracellular signaling cascade is predominantly responsible for this effect? A) cAMP-PKA pathway B) IP3-DAG pathway C) cGMP pathway D) MAPK pathway E) MLCK pathway

The correct answer is A) cAMP-PKA pathway. Stimulation of beta-1 adrenergic receptors activates the Gs protein pathway, leading to increased adenylate cyclase activity and elevated cyclic adenosine monophosphate (cAMP) levels. This activates protein kinase A (PKA), which enhances myocardial contractility by phosphorylating and thus increasing opening of calcium channels. MLCK is not in cardiac myocytes.

Stimulation of beta-2 adrenergic receptors in bronchial smooth muscle causes bronchodilation. Which secondary messenger molecule is crucial in mediating this effect? A) cAMP B) IP3 C) cGMP D) Ca2+ E) DAG

The correct answer is A) cAMP. Stimulation of beta-2 adrenergic receptors activates the Gs protein pathway. This leads to the activation of adenylate cyclase, which increases cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP levels activate protein kinase A (PKA), which phosphorylates MLCK and inhibits it this in turn leads to bronchodilation via relaxation of bronchial smooth muscle.

Stimulation of which autonomic receptor is responsible for the increased heart rate and force of contraction during the "fight or flight" response? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Muscarinic cholinergic receptors D) Nicotinic cholinergic receptors

The correct answer is B) Beta-1 adrenergic receptors. These receptors are found primarily in the heart and respond to norepinephrine released by sympathetic nerves. Stimulation of beta-1 receptors increases heart rate (positive chronotropic effect) and the force of myocardial contraction (positive inotropic effect).

Activation of alpha-1 adrenergic receptors in vascular smooth muscle leads to vasoconstriction. Which intracellular second messenger pathway is primarily involved in this response? A) cAMP-PKA pathway B) IP3-DAG pathway C) cGMP pathway D) MAPK pathway

The correct answer is B) IP3-DAG pathway. Activation of alpha-1 adrenergic receptors involves the Gq protein pathway. This leads to the activation of phospholipase C (PLC), which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers release of intracellular Ca2+, leading to vasoconstriction.

Activation of M2 muscarinic cholinergic receptors in the heart leads to hyperpolarization and decreased heart rate. Which ion channel is primarily involved in this process? A) Sodium channel B) Potassium channel C) Calcium channel D) Chloride channel E) Magnesium channel

The correct answer is B) Potassium channel. Activation of M2 muscarinic cholinergic receptors stimulates the G protein-gated inwardly rectifying potassium (GIRK) channels. Opening of GIRK channels allows efflux of potassium ions, leading to hyperpolarization and slower heart rate (bradycardia).

Which autonomic receptor type is responsible for mediating the effects of sympathetic innervation on sweat glands? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Beta-2 adrenergic receptors D) Muscarinic cholinergic receptors

The correct answer is C) Muscarinic cholinergic receptors when activated produce secretions of all types: parasympathetic (salivation, lacrimation, GI, Lungs) and sympathetic (thermo regulatory sweating)

Stimulation of which autonomic receptor leads to increased salivary and lacrimal gland secretion? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Muscarinic cholinergic receptors D) Alpha-2 adrenergic receptors

The correct answer is C) Muscarinic cholinergic receptors. These receptors are present in salivary and lacrimal glands. Activation of muscarinic receptors by acetylcholine results in increased secretion of saliva and tears.

Which autonomic receptor subtype is found at the neuromuscular junction of skeletal muscles? A) Alpha-1 adrenergic receptors B) Beta-1 adrenergic receptors C) Nicotinic cholinergic receptors D) Muscarinic cholinergic receptors

The correct answer is C) Nicotinic cholinergic receptors. These receptors are present at the neuromuscular junction between motor neurons and skeletal muscle fibers (somatic part of the peripheral nervous system). Activation of nicotinic receptors by acetylcholine initiates muscle contraction.

What might be expected if a patient who is on a beta-blocker to treat his hypertension suddenly stops using the drug?

This patient may have an accelerated heart rate (tachycardia) that may result in an arrhythmia. This would be a produce of cardiac myocytes up-regulating beta-1 adrenergic receptors. If the drug is stopped to quickly the released norepinephrine will be able to activate cardiac responses more readily.

Which of the following is drug when provided to an animal model will produce a decrease in HR when given alone but when given after administration of a ganglion blocker (cholinergic-nicotinic-receptor antagonist) will have no effect on HR? Acetylcholine Norepinephrine Vasoconstrictor agent Beta Agonist Muscarinic antagonist

Vasoconstrictor agent Drugs can decrease the heart rate directly by activating cholinergic (M2) receptors and or by producing vasoconstriction (alpha-adrenergic receptor activation) which in turn will cause the autonomic reflex via the barro stretch receptors to activate a neural increase in parasympathetic pre-ganglionic that activate post ganglionic neurons that in turn release acetylcholine the endogenous activator of M1 receptors. In this case a vasoconstrictor agent (most likely a selective alph1-1 receptor agonist) produces the autonomic reflex to increase parasympathetic response. In the presence of a ganglion blocker that parasympathetic response is blocked and and no autonomic input is received by the heart.

Vasodilation will produce what effects on heart rate?

Vasodilation will produce a feedback response to the brain resulting in an increase in sympathetic outflow from brain to heart. Activated sympathetic neurons will release more norepinephrine that in turn will stimulate beta-1 receptors on cardiac pacemakers cells to increase heart rate. More heart rate = higher blood pressure.

Which of the following is drug when provided to an animal model will produce a increase in HR when given alone but when given after administration of a ganglion blocker (cholinergic-nicotinic-receptor antagonist) will have no effect on HR? Acetylcholine Norepinephrine Vasodilator agent Beta Agonist Muscarinic antagonist

Vasodilator agent (alpha-antagonist, calcium channel blocker, nitric oxide, etc.) Drugs can increase the heart rate DIRECTLY by activating beta-1-adrenergic receptors located on heart-cells and or by producing vasodilation which in turn will cause the autonomic reflex via the barro stretch receptors to activate a neural increase in sympathetic pre-ganglionic that activate post ganglionic neurons that in turn release norepinephrine the endogenous activator of beta-1 receptors (see diagram for reflex schematic). In this case administration of the vasodilator stimulates the INDIRECT sympathetic response which out competes the direct response on the heart. The ganglion blocker prevents sympathetic response. Acetylcholine is a muscarinic agonist that would have produced a decrease in the heart rate if administered with a gagnlion blocker.

What is the physiologic response to a sudden increase in blood pressure?

When blood pressure increases it results in the activation of baro-receptor "stretch receptors". An afferent signal travels back through the spinal cord to the brain which results in stimulation of medullary centers to increase parasympathetic and decrease sympathetic efferent outputs to the heart. The net result is a decrease in heart rate and the following drop in blood pressure. In contrast, when blood pressure is decreased the signal that stimulates parasympathetic medullary outputs are decreased while the sympathetic pathway becomes disinhibited allowing it to increase heart rate and vascular tone.

Diastolic blood pressure is not influenced by (cardiac output) CO since it is the blood pressure after contraction and is; therefore, influenced by the vascular blood volume and space only, which equals __________-one receptor constricting influences minus _________-2 receptor or NO-relaxing-influences. Note, beta one effects are not important in controlling diastolic BP.

alpha-1 adrenergic (vasoconstrictive influences) beta-2 adrenergic (vasodilative influences)

What type of receptor is located on organs innervated by sympathetic neurons when it is functionally important to produce smooth muscle contraction (radial muscles of the eye, organ blood vessels, gut and urinary sphincters)?

alpha-1 adrenergic receptors

What are the names of the autonomic receptors that are activated by the neurotransmitter--norepinephrine?

alpha-1, 2 adrenergic receptors beta-1, 2 adrenergic receptors

What autonomic receptor can produce an increase in calcium influx into cardiac myocytes?

beta-1 adrenergic receptors. Norepinphrine produces an inc. in contractile force and rate by activating beta 1-adrenergic receptors. All beta-adrenergic receptors are coupled to the g-protein, Gs, which activates adenylyl cyclase (AC)--the enzyme that produces the intracellular 2nd messenger, cAMP . The raise in intracellular cAMP increases both heart rate and contractile force by promoting an inc. in intracellular calcium levels. Activated PKA produces an inc. in intracellular Ca++ by phosphorylating membrane bound voltage gated Ca++ channels (Cav1,3) allowing more Ca++ entry into the cell and by phosphorylation and subsequent opening of the ryanodine receptor (RYR) located on the sarcoplasmic reticulum (SR), which releases Ca++ from this storage compartment

An increase in glucose production, which is required for energy expenditure, is produced by norepinephrine activation of beta_________ receptors located on liver cells.

beta-2 adrenergic receptors

What type of receptor is located on organs innervated by sympathetic neurons when it is functionally important to produce smooth muscle relaxation (bronchioles, bood vessels in skeletal muscle, gut and bladder walls)?

beta-2 adrenergic receptors

Activation of the intracellular protein, Gs, leads to the production of what intracellular second messenger?

cAMP

What may happen when GPCR receptors are continually exposed to receptor antagonist?

cellular adaptation may involve increasing the number of receptors on the cell surface (up regulation)

A muscarinic-receptor agonist will do what to heart rate in the presence of a ganglion blocker?

decrease heart rate (direct binding to M2 receptors on SA and AV nodal cells), which when activated hyper polarizes myocytes.

Vasodilation induced increases in heart rate can be blocked by what two types of receptor antagonist?

ganglionic blockers (nicotinic-receptor antagonist) and beta-1 receptor antagonists

A beta-agonist will do what to heart rate in the presence of a ganglion blocker (nicotinic receptor antagonist)?

increase heart rate (direct binding to beta-1 receptors on the heart

What are common locations for beta-2 adrenergic receptors?

lungs, blood vessels of skeletal muscle, uterus, bladder and GI walls

Peripheral Cholinergic Neurons

neurons that synthesize and release acetylcholine. 1) Pre-ganglionic sympathetic, sympathetic neurons that innervate the adrenal medulla and parasympathetic neurons (both pre and post ganglionic) 2) somatic muscle (motor) neurons

Sympathetic neurons exit the tharocolumbar region of the spinal chord. These neurons synthesis, store and release ________________________as their classic neurotransmitter. This type of neuron is defined as a ______________ neuron.

pre ganglionic sympathetic neurons synthesize and release acetylcholine, which are defined as cholinergic. Post-ganglionic sympathetic neurons vary. They can be cholinergic (thermoregulatory sweating), noradrenergic (a neuron that synthesizes and releases norepinephrine), or dopaminergic (synthesize and release dopamine)

What is the mechanism involved when alpha-2 receptors are activated to reduce neurotransmitter release?

remember the mnemonic MAD2. All receptors M2, Alpha2 and dopamine-2 couple to the G protein Gi. The activation of Gi has two principle intracellular effects. 1) to inhibit andenylyl cyclase (less cAMP, less PKA activation, less calcium entry into heart or nerve cells) 2) increase the outflow of potassium resulting in hyper polarization. In heart cells this means slower heart rate. In nerve cells this means less synaptic vesicle release of neurotransmitters (calcium is required for docking and fusion of synaptic vesicles with plasma membrane). In summary, the cascade results in less calcium entry and less release of norepinephrine.

What might be expected if a patient who is on an alpha-2 adrenoceptor agonist stops taking the drug suddenly?

severe hypertension. This response may be produced via a compensatory decrease in presynaptic alpha-2 receptors (pathways involved in decreasing norepinephrine release) and and upregulation of post-synaptic sympathetic receptors like (beta-1 and alpha 1)