Neurotransmitters & Receptors Chp 4

Norepinephrine: Synthesized

• from dopamine •Released into bloodstream (adrenal medulla)

Noradrenaline

- affects attention and responding actions in the brain, and involved in fight-or-flight responses - contracts blood vessels, increasing blood flow

GABA

- calms firing nerves in CNS - high levels improve focus - low levels cause anxiety - also contributes to motor control and vision

Serotonin: what it does

- contributes to well-being and happiness - helps sleep cycle and digestive system regulation affected by exercise and light exposure

Dopamine: what it does

- feelings of pleasure, and also addiction, movement, and motivation - people repeat behaviors that lead to dopamine release

Acetylcholine

- involved in thought, learning, and memory - activates muscled action in the body - also associated with attention and awakening

Glutamate

- most common brain neurotransmitter - involved in learning and memory - regulates development and creation of nerve contacts

Adrenaline

- produced in stressful or exciting situations - increases heart rate and blood flow, leading to a physical boost and heightened awareness

Endorphins

- released during exercise, excitement, and sex - producing well-being and euphoria - reducing pain, biologically active section shown

Norepinephrine

•A neurotransmitter involved in arousal, as well as in learning and mood regulation •Responsible for the fight-or-flight response to stressful situations •Chemicals that cause your heart to beat faster, emotions to change instantly (fear/threat), sending more blood flow to your skeletal muscles, retaining sodium, etc. •Main NT of body's sympathetic nervous system •Produced from dopamine •Functions in brain and body as hormone and neurotransmitter •Produced by the adrenal medulla in the adrenal glands (hormone) •Sympathetic nerve terminals (NT) •Found in locus coeruleus in brain stem •"stress hormone" •Released into blood as a stress hormone when brain perceives that a stressful event has occurred

Other NT

•Acetylcholine •Histamine

Norepinephrine: Receptor Sites

•Alpha •Beta

Adrenergic receptors: Alpha

•Alpha 1 (excitatory) •when stimulated, responsible for constriction of blood vessels (high blood pressure), dilation of pupil, etc. •Alpha 2 (inhibitory) •when stimulated can cause suppression of norepinephrine and epinephrine

Neuropeptide Y (NPY)

•Also found in hypothalamus •Release of it causes increase in eating, being a powerful stimulator of food intake •Disturbance of this NT may be related to some eating disorders

Glutamate

•Amino acid •Important neurotransmitter found throughout the cerebral cortex •Most commonly found NT in the nervous system •Main function: transmit information that regulates brain development and determines cellular survival •At normal concentrations, crucial for brain functions such as learning and memory •Excitatory transmitter •increases likelihood that nerve cell will fire an action potential •Involved in consciousness •Mostly produced during daytime •Can be found in foods: meats, dairy, eggs, high protein vegetables •Important role in synaptic plasticity

Serotonin: Synthsized

•Amino acid L-tryptophan which is converted serotonin via 5-Hydroxytryptophan (5-HTP) along a metabolic pathway involving two enzymes, tryptophan hydroxylase and amino acid decarboxylase. •Cannot pass blood-brain barrier but tryptophan can at times

Endogenous Opioids: Noiceptin

•Anti-analgesic (increases pain perception by blocking action of opioids) •Helps to protect against physical effects of stress

Adrenergic receptors: Beta

•Beta 1 •Fast heartbeat (tachycardia), increased breakdown of fat, etc. •Beta 2 •Increase of glucose, widening of blood vessels (vasodilation), etc. •Beta 3 •Relax urinary bladder and generation of body heat

Blood Brain Barrier

•Blood vessels (capillaries) that selectively let certain substances enter the brain tissue and keep other substances out •Protect brain from "foreign substances" (toxins or pathogens) in the blood that may injure the brain (cause brain infections) while allow nutrients to reach the brain •Certain molecules can get through the blood brain barrier

Neurotransmitters

•Chemical agents released from presynaptic bulb into the synaptic cleft •Over 100 chemical messengers •Body's messengers •In order for a neuron to communicate with another neuron, signal needs to cross the synapse and these signals are the NT •Most NT fall into three main groups •Amines •Amino acids •peptides •Think of NT as keys and receptors as locks •NT locks into the receptor site •Same NT produces different effects by binding to different receptors

Neurotransmitter vs. Hormones: NT

•Chemical messenger •Only occur in nerve cells •Travel across synapse

Neurotransmitter vs. Hormones: HM

•Chemical messengers •Travel through bloodstream •Endocrine glands and reproductive organs make and secrete range of hormones

Histamine

•Chemical stored in mast cells that triggers dilation and increased permeability of capillaries •plays a role in metabolism, temperature control, regulating various hormones, and controlling the sleep-wake cycle, amongst other functions •Cannot cross blood—brain barrier

Peptides NT

•Cholecystokinin •Neuropeptide Y •Vasoactive intestinal peptide •Substance P and Substance K •Somatostatin

Vasoactive Intestinal Peptide (VIP)

•Digestive system peptide •involved in circadian rhythms (natural daily rhythms of the body)

Receptor Site: Function

•When NT binds to the receptor site, the receptor site changes shape •Will result in either excitatory or inhibitory action potential

Endogenous Opioids

•Endogenous opioids = proteins produced under pain or stress conditions that block pain at either spinous (spinal cord) or supraspinous (brain stem) levels •Enkephalins •Produced in response to minor pain, analgesic effect of about 2 minutes •Basal ganglia, limbic system, brain stem, and upper spinal cord •Beta-endorphin •Produced in response to more severe pain with analgesia effect of around 4 hours •Thalamus, hypothalamus, and brain stem

Acetylcholine

•First neurotransmitter to be discovered •Plays a role in PNS and CNS •Responsible for stimulation of muscles •Used by autonomic nervous system such as smooth muscles of the heart •only neurotransmitter that sends and receives information between the motor neurons and voluntary muscles (muscles you have conscious control over, such as the biceps) •This means that every move you make depends on the release of ACh from your motor neurons to your muscles to make the move •Example: walking, talking, typing •Learning and memory formation •Depletion = Alzheimer's

Cholecystokinin (CCK)

•Found both in digestive tract (where it regulates emptying gall bladder) and the brain •In the hypothalamus: regulating the inhibition of food intake once stomach is full (satiation) •In cerebral cortex: linked to memory, cognition, mother-infant relationship, and pain threshold regulation •Recently of interest due to linking NT to several mental health disorders including anxiety, depression, and psychosis

Somatostatin

•Found in sympathetic nervous system and thalamus •In brain: has a sedately effect and increases the action of sedately drugs such as barbiturates •Appears to reduce rate of firing of neurons, suppresses motor activity and inhibits release of growth hormone

Endogenous Opioids: Endomorphines

•Found in thalamus, Hypothalamus, and basal ganglia

Substance P

•Functions on the main pathways from the periphery to the spinal cord (afferent neuron) •Brain: concentrated in substantia nigra (dopaminergic neurons) and hypothalamus (serotonin neurons)

GABA: Receptors

•GABAa •GABAb

Amino Acid NT

•Glutamate •GABA •Aspartate •Glycine

Endogenous Opioids: Dynorphins

•Hypothalamus and brain stem

Acetylcholine: Broken down

•Into choline and acetate by enzyme acetylcholinesterase •Reuptake •The remainder is excreted

Dopamine: Receptors

•Low dose D1 agonist. Med dose B1 agonist. High dose Alpha 1 agonist •D1 and D5 : excitatory •D2, D3, and D4: inhibitory

Glutamte: Receptors

•NMDA •Need more persuasion for a rapid responses •AMPA •Rapid responses

Acetylcholine: Receptors

•Nicotonic •Muscarinic •Controlling body muscles but also found in brain

Proteins

•Nutrients the body uses to build and maintain its cells and tissues •Proteins are essential nutrients found in healthy diet •formed by amino acids •Each protein has a specific job to create

Receptor Site: Location

•Postsynaptic receptors •Part of the postsynaptic membrane •function: effect some kind of change within the postsynaptic cell •i.e. generation of new action potential •Autoreceptors •Found on presynaptic membranes or other parts of neuron •Function: provide feedback information to the neuron at presynaptic bulb •To regulate (or control) further NT release

•Referred to as "building blocks" of life •All proteins are made of building blocks called amino acids •Not all proteins in diet contain amino acids you require •To make all proteins in body, you require 22 different amino acids •They are considered essential which means you can't synthesize them in your body and must obtain them from food •Other amino acids are nonessential: meaning you can manufacture them yourself from fats, carbohydrates, and other amino acids •Think of amino acids as train cars that make up an entire train called a protein

•Referred to as "building blocks" of life •All proteins are made of building blocks called amino acids •Not all proteins in diet contain amino acids you require •To make all proteins in body, you require 22 different amino acids •They are considered essential which means you can't synthesize them in your body and must obtain them from food •Other amino acids are nonessential: meaning you can manufacture them yourself from fats, carbohydrates, and other amino acids •Think of amino acids as train cars that make up an entire train called a protein

Dopamine: Broken down

•Reuptake •Degraded by enzymes •monoamine oxidase (MOA) •homovanillic acid excreted by cerebrospinal fluid

Serotonin: Broken down

•Reuptake •Enzymes responsible are MAO and aldyhdee oxidase resulting in metabolite (waste product) •Firs through CSF, then to blood, then carried to kidneys •Serotonin can be measured in your urine

What happens after NT completes its job

•Reuptake •NT returns to the presynaptic neuron •Diffusion •Drifts away, out of the synaptic cleft where it can no longer act on a receptor •Enzymatic degradation •a specific enzyme changes the structure of the neurotransmitter so it is not recognized by the receptor •Acetylcholine broken down into choline and acetate

Norepinephrine: Broken down

•Reuptake •Enzymes MOA

Peptide

•Short chain of amino acids linked by peptide bonds •Naturally occurring biological molecules •Amino acids are linked together in proteins by a special kind of bind, the peptide bond

GABA info

•Synthesized from glutamate •Important neurotransmitter found throughout the cerebral cortex •Inhibitory neurotransmitter •Low level in some areas of brain is implicated as part of the cause of epilepsy •Anticonvulsants (drug treatment) targets the enzymes that regulate GABA production and increase GABA levels at the synapse •GABA receptor •Blocks action potential and reduce overall activity of the brain •GABAa receptor is the site of binding for several important drugs including benzodiazepines and barbiturate, as well as binding alcohol •Depletion = anxiety

GABA: Synthesized

•Synthesized from glutamate •Its synthesis also requires a supporting chemical - a cofactor - called pyridoxal phosphate, which is derived from vitamin B6 taken in from your diet •Difficult to cross blood-brain barrier

Acetylcholine: Synthesized

•Synthesized in the brain by enzyme choline •Choline from dietary sources must be delivered to the brain by blood

Glutamate: Broken down

•Taken into a nearby cell to make suer level of glutamate in synapse doesn't become too high •Next it can be either recycled or converted back into glutamine

GABA: Broken down

•Taken up by transporter proteins which remove it from the synaptic space and store it either in the surrounding neurons, or the supporting glial cell •Within the cell, GABA is then broken down into the metabolite succinate by two sequential enzymes the first one being GABA-transaminase, followed by succinic semialdehyde dehydrogenase

Glutamate Toxicity

•Too much = nerve cell receiving signals can become overexcited •Kills neurons by overexciting them •Ex: head injury or stroke, glutamate floods injured area and kills neurons by overexciting them causing brain damage •Low levels = oversensitive

What happened if NT fails at its job

•Too much may be released into the synapse •Too many NT may be deactivated by enzymes •Reabsorbed too quickly •Possible mental health diagnosis •Can be altered as a result of drug use

Dopamine: Synthesis

•Uptake of tyrosine via sodium-independent transporter system-L. RLE isTyrosine to L-DOPA by tyrosine hydroxyase. •Tyrosine -> L-DOPA -> Dopamine •Synthesized (made/produced) from L-Dopa which is generated from the amino acid tyrosine •Cannot cross blood-brain barrier and has to be synthesized inside the brain

Serotonin

•a compound present in blood platelets and serum that constricts the blood vessels and acts as a neurotransmitter •Found in brain and digestive system •Found in the raphe nuclei in the brain stem (and other areas) •Influence over a wide range of brain functions including regulation of mood, movement, appetite, sexual activity, and sleeping •Vital role in maintenance of mental health •Found through dietary amino acid tryptophan. This amino acid must enter your body through your diet •Nuts, cheese, red meat •Mood •Low levels = mental health •Digestion: bowel movements (found in stomach and intestines) •Nausea: help remove bad food or other substances from the body •Sleep: stimulate parts of brain that control sleep and waking •Blood clotting: related to help heal wounds •Bone health: high levels = osteoporosis

Dopamine

•a neurotransmitter that regulates motor behavior, motivation, pleasure, and emotional arousal •Found in two areas of the brain: substantia nigra (movement) and ventral tagmental areas (VTA) (reward) and pass to specific brain areas •pleasure: reward pathway •Negative way: associated with drug addiction •Positive way: Eating, sex •Can also act as an inhibitory NT •Inhibiting muscle tone: Parkinson's Disease •Fail to produce dopamine •Place essential role in coordination of body movement •Inhibits breast milk production: block release of hormone prolactin (pituitary gland) •Too much = schizophrenia/hallucinations

Enzyme

•a substance produced by a living organism that acts as a catalyst to bring about a specific biochemical reaction •Protein used to speed up the rate of a chemical reaction

Serotonin: Receptors

•at least 9 receptor subtypes •Form many classes and subclasses •Addiction •Aggression •Anxiety •Appetite •Cognition •Impulsivity •Learning

Neurotransmitter Influences: Inhibitory

•block the signal from carrying a message •Decrease the likelihood of neuron to fire action potential •Tells brain "not to fire" •Example: GABA

Glutamate: Synthesized

•from molecule glutamine

Catecholamines

•hormones secreted by the adrenal medulla that affect the sympathetic nervous system in stress response •Most common (Come from amino acid tyrosine) •Dopamine •Noradrenaline (norepinephrine) •Adrenaline (epinephrine)

Adrenergic receptors

•receptor sites for the sympathetic neurotransmitters norepinephrine and epinephrine •Receptors that get activated when they bind to catecholamines

Adrenaline (Epinephrine)

•secreted by the adrenal medulla; increases heart rate and blood pressure •Known as a hormone (but far less understood as neurotransmitter) •NT within the brain, helps neurons to communicate with one another •Mainly produced by adrenal glands (adrenal medulla) and has functions peripheral (outside of the brain), therefore can also be considered hormone •Brain perceives danger > amygdala triggers hypothalamus to activate autonomic nervous system > signals from autonomic nervous system stimulate adrenal glands to start pumping epinephrine into bloodstream

Neurotransmitter Influences: Excitatory

•signal the change to occur •Increase the likelihood of neuron to fire action potential •Tells brain to "fire" •Example: Glutamate