L1 - NT systems Flashcards by megan falco

where is ACh found in CNS

interneurones of the striatum
nucleus basalis pathways
septohippocampal pathway

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where is ACh found in periphery

lower motor neuornes
GI tract 
all preganglionic SNS nerves 
all PNS nerves 
retina

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where does ACh synthesis occur

cytoplasm of nerve terminal

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describe synthesis of ACh

choline + acetyl CoA -> ACh

(via choline acetyltransferase

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where is choline acetyltransferase synthesised? (ChAT)

cell body, then transported to nerve termminals

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where does choline come from for ACh synthesis?

where does Acetyl CoA come from for ACh synthesis?

diet or recycled from breakdown of ACh

krebs cycle

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describe storage of ACh

VAChT (vesicular ACh Transporter) antiports 1x ACh+ into the vesicle and 2xH+ out of the vesicle

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what is the [ACh] inside the vesicle and in cytoplasm

inside 1000mM

cytoplasm 1mM

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is ACh release Ca dependant?

yes

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what are the 3 types of vesicle pools? and describe them

releasable -> fused to membrane and ready to release NT
recyclable -> returning to collect NT, transporters and synaptobrevin being re-added to mmebrane
reserve -> not in use

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briefly describe what type of receptor the nicotinic ACh receptor is
- how many subunits

ligand gated ion channel

5 (pentameric)

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where are NAChRs found?

muscle
embryonic muscle
ganglion
CNS

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what type of NAChRs are found in ganglion?

alpha 3 and beta 4

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what NAChRs are found in CNS

a4 , a7 , B2

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what type of receptors are the MAChRs

GPCRs (class A,, rhodopsin like)

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what G protein is coupled to M1 receptors

Gq/G11

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what G protein is coupled to M2 receptors

Gi/Go

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what G protein is coupled to M3 receptors

Gq/G11

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what G protein is coupled to M4 receptors

Gi/Go

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what G protein is coupled to M5 receptors

Gq/G11

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where is ACh degraded?

in the synaptic cleft

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describe breakdown of ACh

ACh -> choline + acetic acid

Via acetylcholinesterase

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describe ACh reuptake process

once broken down to choline, the choline transporter transports choline back into presynaptic terminal (recycling)

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name agonists of nAChRs

suxamethonium

nicotine

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name antagonist of nAChR

pancronium

name agonist of mAChR

muscarine

function of hemicholinium?

blocks reuptake of choline

name a drug that blocks ACh degradation

rivastigmine

list some diseases involving ACh

``` parkinsons (motor control) myasthenia gravis (NMJ) ```

what type of NT is dopamine

monoamine

where is DA founnd in CNS?

nigrostriatal pathway mesolimbic and mesocorticol pathway tubero-hypophyseal pathway

where is DA found in the periphery

retina

where does DA synthesis occur

cytoplasm of nerve terminal

describe process of DA synthesis

tyrosine -> DOPA (via tyrosine hydroxylase) | DOPA -> dopamine (via dopadecarboxylase)

what is the rate limiting step in DA synthesis

tyrosine -> dopa via tyrosine hydroxylase

where can we get tyrosine from

diet

what is the name of the transporter that transports DA into vesicle

VMAT (1 or 2) vesicular monoamine transporter

describe locations of VMAT 1&2

vesicular membrane | cell specific, certain cells contain each one

describe storage of DA

VMAT1/2 transport DA + in turn for 2x H+

how is high [H+] maintained within vesicles?

ATPase pump

is DA release Ca dependant

yes

describe release of DA (not process)

released from terminal and en passant variscosities | DA released all the way along the axon

what are en passant variscosities

regions along the axon that can release NT (not the terminal)

list NTs that are released from en passant variscosites aswell as the terminal

DA | NA

what type of receptors are DA receptors

GPCRs (class A, rhodopsin like)

how many subtypes of DA are there and what are they

5 D1 like -> excitatory D2 like -> inhibitory

what are D1 -like receptors coupled to

what DA receptors are considered D1 like?

D1, D5

what DA receptors are considered D2-like

D2 D3 D4

what are D2 like receptors coupled to

Go/Gi

describe re-uptake of DA

reuptake via co-transporter DAT (dopamine active transporter) along with Cl- and 2Na

what is the end product for the breakdown of DA

homovanillic acid

name a drug that can block stroage of DA

reserpine

agonists of DA

apomorphine

antagonist of DA

chlopromazine

what effect does cocaine have on DA?

blocks reuptake of DA

what drug classes can block DA degradation (give examples)

``` MAO inhibitors (selegiline) COMT inhibitors (entacapone ```

what is COMT

Catechol - O - methyltransferase

list some diseaeses involving DA

parkinsons drug dependance (reward process) schizophrenia (thought)

what enzymes degrade DA

MAO monoamine oxidase | COMT - Catechol - O - methyltransferase

what NTs are monoamines

DA | NA

where is NA found in brain

many locations, including - cerebellum - brainstem and spinal cord - amigdyla - hypothalamus - substantia nigra - locus coeruleus

where is NA found in periphery

postganglionic SNS nerves | retina

describe synthesis of NA

tyrosine -> DOPA (tyrosine hydroxylase) DOPA -> DA (dopa decarboxylase) DA -> NA (dopamine B hydroxylase)

where is dopamine B hydroxylase found

only in the vesicles of noradrenergic neurones

where is NA synthesised

DA is synthesised in cytoplasm then is converted to NA in the vesicle

describe NA storage

same as DA, via VMAT1/2 in exchange for 2H+

describe release of NA

Ca dependant released from terminals and en passant variscosities often co released with ATP

what is NA often co released with?

ATP

what type of receptors are NA receptors

GPCRs (class A, rhodopsin like)

what are a1 NA receptors coupled to

Gq/G11

what are a2 NA receptors coupled to

Gi/Go

are a1 pre or post synaptic

post

does adrenaline or NA have higher affinity for a1 receptors

are a2 NA receptors pre or post synaptic

presynaptic

does adrenaline or NA have higher affinity for a2 receptors

adrenaline

what are B1, B2 and B3 NA receptors coupled to?

do B1 B2 B3 NA receptors have higher affinity for NA or adrenaline

- ß1 - NA > Ad - ß2 - Ad > NA - ß3 - NA = Ad

describe re uptake of NA

Uptake 1 - back into neurone via NET (norepinephrine co-transporter) Uptake 2 - into glial cells (astrocytes) via NET

describe the NA re-uptake transporter

NET - norepinephrine transporter | co transports NA along with Cl- and Na+ into the terminal or astrocytes

what uptake method for NA is into astrocytes?

uptake 2

what is the final product in the breakdown of NA

VMA -> vanillylmandelic acid

where is NA excreted?

in the urine as vanillylmandelic acid

what enzymes breakdown NA

MAO | COMT ( catechol - O - methyltrannsferase

name a a1 agonist of NA

clonidine

name a B2 NA agonist

salbutamol

name a B NA antagonist

propranalol

name a a1 NA antagonist

prazosin

name drug classes that block NA reuptake and give example

NSRI (NA selective re-uptake inhibitors) - reboxitine TCAs (imipramine) cocaine amphetamine

list diseases NA is involved in

hypertension (SNS, CV control)

what type of NT is 5-HT

indolamine

where is 5-HT found in brain

``` hippocampus & amygdala raphe nuclei cerebellum hyppothalamus & thalamus & striatum Substantia nigra ```

where is 5-HT located in the periphery

enteric nervous system retina platelets

where is serotonin synthesised

cytoplasm of nerve terminal

describe synthesis of serotonin

tryptophan -> 5-hydroxytryptophan ( tryptophan hydroxylase) | 5-hydroxytryptophan -> 5-hydroxytryptamine (dopa decarboxylase

what does 5-HT stand for

serotonin | 5-hydroxytryptamine

is serotonin released from en passant variscosities?

can serotonin be co released?

yes, with somatostatin / substance P

what type of receptor is the 5-HT3 receptor

ligand gated ion channel (mixed cation)

what serotonin receptor subtypes are coupled to Gs?

5HT-4 5-HT6 5-HT7

what serotonin receptor subtype is found presynaptically and what does it couple to?

5-HT1 | Gi/Go

what does 5-HT2 receptor couple to?

Gq/G11

describe re-uptake of 5-HT

SERT (serotonin reuptake transporter) co transports 5-HT into terminal along with Cl- and 2Na+

describe degradation of 5-HT

5-HT -> 5-hydroxyindolealdehyde (via monoamine oxidase) | 5-hydroxyindolealdehyde -> 5-hydroxyindoleacetic acid 5-HIAA (via aldehyde dehydrogenase)

5-HT3 antagonist

ondansetron

name drug classes that block the re-uptake of 5-HT and give examples

SSRIs (citalopram) TCAs (imipramine) Amphetamine

list other NTs (9)

``` bradykinin ATP substance P glycine Glutamate NO histamine GABA neuropeptide Y ```

L1 - NT systems Flashcards

(107 cards)