CNS Neurotransmitters Flashcards by C H

What are neurotransmitters? What do they produce?

chemical signals from presynaptic nerve terminals where they can bind to receptors on post-synaptic cells;
transient changes in electrical properties of target cell, leading to variety of effects

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What are the 2 major types of neurotransmitters?

small molecules and neuropeptides

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Give examples of small molecules neurotransmitters. Give describe of neuropeptides.

small molecules: ACh, amino acids (glutamate, GABA, glycine), biogenic amines (dopamine, NE, serotonin

neuropeptides: more than 100 types, 3-36 aa long

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How is concentration of neurotransmitter regulated?

neurotransmitter synthesis, packaging, release, and removal

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What does removal of neurotransmitter from the synaptic cleft do?

terminates transmission

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How is the specificity of a neurotransmitter determined by its life cycle?

life cycle specific to each neurotransmitter

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Compare and contrast synthesis and packaging of small molecules and neuropeptides

SM: made in presynaptic terminal, packaged in vesicle transporters; respond fast to increased demand (made in nerve terminal)

NP:made in cell body, packaged, transported along entire axon; cannot respond rapidly to inc demand

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What are the 2 types of neurotransmistter receptors? Describe them.

Ionotropic; ligand-gated ion channels that open in direct response to ligand binding (4-5 subunits); each contanin 3 or 4 transmembrane domains
-multiple subunits can be assembled to generate a diverse set of receptors

metabotropic neurotransmitter receptors
-G protein coupled receptors that activate G-proteins in response to ligand binding

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What allows the ligand to go through the ionotropic receptors?

Confirmational shift allows ions to go through

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How many subunits are combined to make a functional ionotropic receptor?

4 to 5 subunits

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How many transmembrane domains are typically associated with metabotropic receptor? How is their function different from ionotropic receptors?

7; second messenger system used

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Both metabotropic and ionotropic receptors exist as many different types because

it increases diversity of their properties and functions

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What is acetylcholine?

small molecule neurotransmitter that is important for attention, arousal, and reward plasticity

enhances sensory functions upon waking

damage to cholinergic system is associated with the memory deficits in AD

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wherew is Ach found in the PNS? CNS?

PNS: neuromuscular junction
synapses in ganglia of visceral motor system

CNS: interneurons in the brainstem and forebrain
large motor neurons in the basal forebrain that project to cerebral cortex
(function unclear)

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The precursor to ACh is

acetyl coA and choline

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The receptors responding to ACh are

ionotropic and metabotropic receptors

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ACh is removed by____. It’s mechanism is____.

acetylcholinesterase; cleaves ACh into acetate and choline

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Sarin/organophosphates are dangerous to humans because

inhib acetylcholinesterase and cause continued muscular depolarization–>refractory to added ACh–>results in muscular paralysis

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ACh is packaged in

synaptic vesicles by a ACh transporter

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Ionotropic ACh receptors function as____. What do they mediate?

excitatory cation selective channels; mediate synaptic transmission at NMJ

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Compare and contrast neuronal and muscular receptors.

They both have 5 subunits, but have different compositions

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Metabotropic ACh receptors mediate most ACh effects in the _____.

brain

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Where are muscarinic receptors highly expressed?

forebrain

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What is the role of muscarinic recpetors in the periphery?

regulate autonomic effector organs (heart, smooth muscle, etc

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Atropine and scopalomine are useful treatments because they

they are ACh antagonists

Myasthenia Gravis onset occurs in

young women and old men

What are some of the symptoms of myasthenia gravis?

muscle fatigue that worsens late in the day or after repeated exercise; improves with rest diplopia and ptosis difficulty speaking swallowing and chewing weakness and fatigue in arms and legs

Myasthenia occurs due to

autoimmunity; antibodies against nAChR, increased turnover of the receptors -altered structure of NMK because of decreased AChR-->sparse and shallow junctional folds and expanded synaptic cleft

The major treatments for Myasthenia Gravis are

cholinesterase inhbitors, thymectomy, corticosteroids, and immunosuppresants

The most prominent transmitter in the brain is

Glu

Glu is used by nearly all ____ neurons, which make up over____ of all brain synapses`

excitatory; 1/2

How can Glu contribute to negative consequences in the brain?

neuronal death during stroke bc O2 deprivation slows reuptake hypoglycemia, trauma, and repeated intense seizures

Can Glu pass the blood brain barrier?

no, but the glutamine can

The precursor of Glu is

glutamine or transamination of alpha-ketoglutarate

Glu is packaged into

sunaptic vesicles by vesicular Glu transporter

Glu is removed from the synaptic cledt by

high affinity Glu transporters on both the nerve terminal and nearby glial cells

What is the role of glial cells in Glu life cycle

covert Glu back to glutamine and transported out of the cell and into nerve terminals

What are the 3 types of Glu ionotropic receptors?

NMDA, AMPA, and kainate

What is special about NMDA

Ca can pass thru, ion flow is voltage dependent and Gly is required to open the channel

There are ____ classes or metabotropic Glu receptors. When activated they ?

3; increase or decrease excitability of postsynaptic cells

GABA and Gly are the ? GABA is used by Gly is used by

major inhibitory neurotransmitters local interneruons and Purkinje cells of the cerebellum Gly predominantly used at synapses in spinal cord

GABA T is converted to ?

glutamate--->glutamine

GABA is transported by

synaptic vesicles

GABA is removed by

re-uptake into terminal and glia

Decreased GABA can cause

epilepsy

GABA is synthesized from

Glu using PLP from Vit. B6

Gly is synthesized from

Ser in the nerve terminal

Gly is packaged into

synaptic vesicels by the vesicular inhibitory transporter

Gly is removed by

re-uptake into terminal and glia

Gly in excess causes

neonatal diseases characterized by lethargy and mental retardation; transporters are deficient

What types of receptors are used by Glu and GABA

Ionotropic: GABAa and GABAc; Gly; inhibitory Cl channels Metabotropic: GABAb

GABAb produces

inhibitory post synaptic response

GABA angonists include

benzodiazephines

Gly receptors are inhibited by ? | It is used as ?

strychine - rat poison because it causes overactivity in the spinal cord

Activation of ? produces inhibitory post synaptic responses

GABAb

GABA reuptake inhibitors can also be used to treat

anxiety and depression

Glu is made and utilized

relatively ubiquitously across the brain

Biogenic amines are synthesized, but there receptors are

in specific regions of brain, not ubiquitous; ubiquitous

Biogenic amines are critical for maintaining

mental health

80% of brain dopamine found in ? | Receives major input from ?

corpus striatum and substantia nigra

The function of neurons in the substantia nigra

coordination of body movements

What happens when there are decreased levels of dopamine? How is this treated?

neurons degenerate; with L DOPA in the striatum

The midbrain dopamine center projects from the

ventral tegmental area to ventral parts of the striatum

The midbrain dopamine system is involved in

motivation, reward, and reinforcement

When people are on cocaine dopamine levels increase by

their interference with the dopamine transporters

Dopamine plays a minor role in

the cortex; regulates emotional behavior (impulsivity)

NE containing neurons are found in

locus coeruleus and project to a variety of forebrain and brainstem targets

NE regulates

sleep and wakefulness, attention and feeding

In the PNS NE

is a major transmitter of sympathetic motor system

Catecholamine receptors are all

metabotropic

Dopamine receptors act by

activating or inhibiting adenylyl cyclase

Antagonists of dopamine receptors in the medulla used as

anti-emetics

NE receptors are

alpha and beta adrenergic receptors;

Agonists and antagonists of NE are used in

many conditions

Catecholamines are removed by

reuptake into terminal mediated by transmitter specific membrane transporters

cocaine causes an net increase in

dopamine production

amphetamines cause net increase in

NE and dopamine

Serotonin is found in

raphe nuclei in upper brainstem, project widely to the forebrain and brain stem

Serotonin functions to

regulate sleep, eating, arousal, and wakefulness

Drugs used to treat anxiety and depression act on

serotonergic neurons

Serotonin reuptake is mediated by

SERT

Metabotropic serotonin receptors are the

major receptors

Metabotropic serotonin receptors function to ? When impaired they when activated they

mediate emotions, circadian rhythms, motor behaviors and mental arousal cause psychiatric disorders mediate satiety and decreased food consumption

Ionotropic receptors (minority)

non selective excitatory channel; target for many drugs

anti-physchotic drugs

block dopamine receptors suggesting excess dopamine releasemay cause some psychotic illness like schizophrenia

anti-anxiety drugs

MAO inhibitors block breakdown of biogenic amines, inhibitors of serotonin receptors

anti-depressants (3 classes)

MAO inhibitors, tricyclic anti depressents, SSRIs

Peptide neurotransmitters modulate

emotion, perception of pain, stress response

Biological action of peptides determined by

amino acid sequence

What are the 5 categories of amino acid sequences

brain-gut peptides, opioids, pituitary, hypothalmic releasing, miscellaneous peptides

Neuropeptides are synthesized by

cleavage of ER targeting signal from pre-propeptide, processed into propeptides in ER by removal of ER targeting signal, final processing to individual active peptides occurs in vesicels after they bud

peptide neurotransmitters are often coreleased with

small molecule neurotransmitters

peptides are removed from the synaptic cleft by

peptidases

endopeptidases

make more active peptides within the synaptic cleft by endopeptidases

peptides use

metabotrophic receptors

Opoid receptors are

widely distributed, can act as depressants, and morphine is an opioid that is one of the most effective analgesics

CNS Neurotransmitters Flashcards

(96 cards)