L1 - NT systems Flashcards
where is ACh found in CNS
- interneurones of the striatum
- nucleus basalis pathways
- septohippocampal pathway
where is ACh found in periphery
lower motor neuornes GI tract all preganglionic SNS nerves all PNS nerves retina
where does ACh synthesis occur
cytoplasm of nerve terminal
describe synthesis of ACh
choline + acetyl CoA -> ACh
(via choline acetyltransferase
where is choline acetyltransferase synthesised? (ChAT)
cell body, then transported to nerve termminals
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
describe storage of ACh
VAChT (vesicular ACh Transporter) antiports 1x ACh+ into the vesicle and 2xH+ out of the vesicle
what is the [ACh] inside the vesicle and in cytoplasm
inside 1000mM
cytoplasm 1mM
is ACh release Ca dependant?
yes
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
briefly describe what type of receptor the nicotinic ACh receptor is
- how many subunits
ligand gated ion channel
5 (pentameric)
where are NAChRs found?
muscle
embryonic muscle
ganglion
CNS
what type of NAChRs are found in ganglion?
alpha 3 and beta 4
what NAChRs are found in CNS
a4 , a7 , B2
what type of receptors are the MAChRs
GPCRs (class A,, rhodopsin like)
what G protein is coupled to M1 receptors
Gq/G11
what G protein is coupled to M2 receptors
Gi/Go
what G protein is coupled to M3 receptors
Gq/G11
what G protein is coupled to M4 receptors
Gi/Go
what G protein is coupled to M5 receptors
Gq/G11
where is ACh degraded?
in the synaptic cleft
describe breakdown of ACh
ACh -> choline + acetic acid
Via acetylcholinesterase
describe ACh reuptake process
once broken down to choline, the choline transporter transports choline back into presynaptic terminal (recycling)
name agonists of nAChRs
suxamethonium
nicotine
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
Gs
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
NA
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?
Gs
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?
no
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
