762: Intro to Autonomic Nervous System ⭐️
Vesamicol does what?
ACh is transported into small clear vesicles; Vesamicol blocks transporter which leads to neurotransmitter depletion
Acetylcholine - All preganglionic fibers are what type? - Most postganglionic fibers are (sympathetic or parasympathetic) with a few (sympathetic or parasympathetic) postganglionic fibers
Acetylcholine (cholinergic nerve fibers) - All preganglionic efferent autonomic fibers - Most parasympathetic postganglionic and a few sympathetic postganglionic fibers
Thermal sweating - neurotransmitter & receptor involved. Which medication blocks this response?
Ach leads to thermal sweating via M3 receptors. Atropine blocks this response.
Adrenal medullary cells Release a mixture of which two neurotransmitters/catecholamines?
Adrenal medullary cells Analogous to postganglionic sympathetic neurons Releases a mixture of epinephrine and norepinephrine (also ATP and enkephalin)
Adrenergic transmission: Conversion of tyrosine to dopa is _____-_______ and dependent on _____________ ___________ase - inhibited by tryosine analog ____________
Adrenergic transmission: Conversion of tyrosine to dopa is rate-limiting and dependent on tyrosine hydroxylase - inhibited by tryosine analog metyrosine
Adrenoceptors respond to _____________(neurotransmitter); two types: ______-________________ & _______-_______________
Adrenoceptors respond to catecholamines, two types: Alpha-adrenoceptors & Beta-adrenoceptors
Acetylcholine is the endogenous neurotransmitter for which receptors?
All Nicotinic and Muscarinic receptors
Clonidine role in Adenylyl cyclase pathway
Alpha 2 agonist, leads to decrease in cAMP via Gi
Experimental animals treated with reserpine for 3 days experience what?
Animals experience a depletion in adrenergic stores of catecholamines. This is called reserpinized.
Isoproterenol role in Adenylyl cyclase pathway
Beta agonist, leads to increase in cAMP via Gs
Botulinum toxin (Botox)
Blocks ACh release at neuromuscular junction by inhibiting Calcium binding to VAMPs. Release of ACh is dependent on Ca++
Cholinergic receptors respond to _____________ (neurotransmitter); two subtypes (named after alkaloids) are ________ & __________
Cholinergic receptors respond to Acetylcholine; Two subtypes (named after alkaloids) are Muscarine (muscarinic) & Nicotine (nicotinic)
Acetylcholine (ACh) binds to which receptors?
Cholinoceptor; muscarinic or nicotinic
Which function is compromised by anesthesia causing an altered outcome than what may be predicted in an intact subject/patient?
Compromised reflex function, such as during anesthesia, may alter outcome of a predicted reflex in an intact subject! Extra tidbit from slide: Reflex responsiveness to drug effects may still be manifested, even if drug "masks" some effects of endogenous transmitter release
Dopa is converted to dopamine by ______ _____________ase - inhibited by _____________
Dopa is converted to dopamine by dopa decarboxylase - inhibited by carbidopa
Dopamine: is and important transmitter in which branch of the nervous system? It is also released by some peripheral (Sympathetic or parasympathetic) nerve fibers located in which organ's vasculature?
Dopamine: important transmitter in central nervous system also released by some peripheral sympathetic nerve fibers (kidney vasculature)
True or False: No innervation of peripheral vasculature within the CNS
False: No innervation of peripheral vasculature within the PNS!!
Hemicholinium does what?
Hemicholinium blocks synthesis of ACh by blocking uptake of choline; a rate limiting step.
What drug blocks ACh at the nicotinic receptor site within the PNS and SNS?
Hexamethonium
In the adrenal medulla, which type of receptor receives sympathetic preganglionic fibers? What neurotransmitters are then released?
In the adrenal medulla, a modified sympathetic ganglion ( Nn cholinomimetic receptor), receives sympathetic preganglionic fibers and releases epinepherine and norepinepherine (80% and 20%) into the blood
Increased peripheral resistance -> _____________cardia Decreased peripheral resistance -> _____________cardia
Increased peripheral resistance ->bradycardia Decreased peripheral resistance ->tachycardia MAP (mean arterial pressure) is the main variable that is controlled by ANS actions. Anything that alters MAP will stimulate compensatory reactions by the ANS!!
Effects of Epinepherine (increased or deceased action) on airways, cardiac output, muscle contraction and efficiency, fatty acid release, mental alertness, ACTH&TSH, glycogenolysis, intestinal motility
Increased: dilates airways, cardiac output, muscle contraction and efficiency, fatty acid release, mental alertness, ACTH&TSH, glycogenolysis, Decreased: intestinal motility (everything else increased)
Muscarinic receptors associated with Gq
M1 & M3
Muscarinic receptors associated with Gi
M2 & M4
MAO-A (NE & EPI) blocked by which antidepressants? MAO-B (DA) blocked by which antiparkinson drug?
MAO-A: Phenelzine & Tranylcypromine MAO-B: Selegeline
Atropine blocks which receptors?
Muscarinic (M) 1-5 M1: Nerve cells M2: Heart M3: All other peripheral sites
Muscarinic chemoreceptors in endothelial cells are activated by the injection of what? This evokes production and release of what? Does this lead to Vasoconstrcition or vasodilation?
Muscarinic chemoreceptors in endothelial cells are activated by injection of ACh or muscarinic agonists, which evoke production and release of nitric oxide (aka EDRF) eliciting vasodilation (hypotension)
Endothelial cells lining vasculature have which receptors?
Muscarinic cholinoceptors
Parasympathetic nervous system receptors
Muscarinic receptors M (M3 in organs, M2 in Heart)
Acetylcholine is blocked by atropine at which receptor site?
Muscarinic(M) receptor site
Tubocurarine blocks which receptors?
Neuromuscular (Nm), branch of Nicotinic receptors (activated by nicotine from tobacco)
Somatic system receptors and their location. Example of medication that blocks receptors.
Nicotinic receptors (Nm) in skeletal muscle, Rocuronium.
Trimethephan or Hexamethonium block which receptors?
Nn, autonomic ganglia, adrenal medulla, and CNS
Nervous sweating - neurotransmitter & receptor involved. Which medication blocks this response?
Norepinepherine release leads to nervous sweating via alpha-1 receptors. Prazosin blocks this response.
Norepinephrine Most postganglionic fibers are what type? A few (sympathetic or parasympathetic) fibers release which neurotransmitter? (thermoregulatroy sweat glands)
Norepinephrine (adrenergic nerve fibers) Most postganglionic sympathetic fibers A few sympathetic fibers release acetylcholine (thermoregulatroy sweat glands)
Parasympathetic Nervous System (PNS) - (craniosacral outputs) preganglionic fibers terminate in what type of ganglia? Postganglionic fibers originate in ganglia(unspecified) and innervate what?
Parasympathetic Nervous System (PNS) - craniosacral outputs Preganglionic fibers terminate in parasympathetic ganglia Postganglionic fibers originate in ganglia and innervate organs
Three alpha 1 adrenergic agonists; via which pathway?
Phenylepherine Norepinepherine Epinepherine Polyphosphoinositide Pathway
Up-regulation of receptors
Postsynaptic lack of activation. Up-regulation of postsynaptic receptor number and/or affinity
Down-regulation of receptors
Postsynaptic persistent activation. Down-regulation of receptor number, affinity, or coupling.
Which indirect acting sympathomimetic, when used orally to relieve nasal and sinus congestion will produce minimal rebound congestion, unlike topically applied sympathomimetics?
Pseudoephedrine - an indirect agonist
After dopamine is converted to norepinnepherine (NE), NE is released into synaptic cleft. What blocks NE release?
Release of NE is blocked by guanethidine
Sympathetic Nervous System innervation of effector organs is (diffuse/selective); whereas Parasympathetic Nervous System innervation of effector organs is (diffuse/selective).
Sympathetic Nervous System innervation of effector organs is diffuse; whereas Parasympathetic Nervous System innervation of effector organs is selective.
Blood vessels are only innervated by which branch of the ANS?
Sympathetic nervous system
Sympathetic nervous system: (thoracolumbar outputs) preganglionic fibers terminate where? Postganglionic fibers innervate which tissues?
Sympathetic nervous system: thoracolumbar outputs, preganglionic fibers terminate in ganglia (paravertebral chains) Postganglionic fibers innervate peripheral tissues
Which drugs are likely to cause rebound nasal congestion brought on by extended use of which medications?
Topical decongestant nasal sprays: oxymetazoline phenylepherine xylometazoline naphazoline
______________ and ____________ displace norepinepherine from vesicles. Tyramine enters via ____________ (___)
Tyramine and amphetamines displace norepinepherine from vesicles. Tyramine enters via Uptake 1 (NET)
Uptake 1 (NET), which transports _______________ into ___________ neuron, is inhibited by __________ (and ___s) which potentiates transmitter activity because Uptake 1 (NET) is the major mechanism to ____________ transmitter action!
Uptake 1 (NET), which transports catecholamines into presynaptic neuron, is inhibited by cocaine (and TCAs) which potentiates transmitter activity because Uptake 1 (NET) is the major mechanism to terminate transmitter action!