BMS11004 - WEEK 3 FLIPPED LECTURE Flashcards
what is acetylcholine made from
Acetyl group + choline, via ChAT (enzyme lives in cytoplasm of presynaptic cholinergic neurons)
how is acetylcholine broken down in synaptic cleft, and by what
by AchE (acetylcholinesterase), into acetic acid and choline
choline is taken up into presynaptic cell by choline transporters and recycled
what 2 type of receptors does acetylcholine act on
ionotropic nicotinic
metabotropic muscarinic
where are nicotinic receptors found, and when opened what do they allow
neuromuscular junctions
ACh-gated Na/Ca channels
when open, allows positive currents in, depolarising neurons
where are muscarinic receptors found, and what are they used for
in CNS, ANS, used in digestion and HR
5 types of GPCRs
M1,3,5 = excitatory
M2,4 = inhibitory
why are muscarinic receptors more present than nicotinic receptors
10-100x more mAChRs, than nAchRs as more important for cholinergic signalling
acetylcholine is a common target for many drugs. how may they impact acetylcholine
- block release
- block Acetylcholinesterase (disrupting Ach breakdown)
- activate acetylcholine receptors
- block receptors
how many botulinum toxin block release of acetylcholine
prevent vesicle fusion by destroying SNARE protein so stop release from motor nerves = stop muscle contraction
how can black widow spider venom (latrotoxin) block release of acetylcholine
cause large calcium influx. first increases Ach release at NMJ, then eliminates it = cause paralysis
how does nerve gas block acetylcholinesterase so disrupt break-down of acetylcholine
AChE inhibitor messing up signalling of parasympathetic nervous system
too much ACh
how can organophosphate pesticides block acetylcholinesterase so disrupt breakdown of acetylcholine
insect main NT is ACh
too much excitation = seizure
how can blocking acetylcholinesterase (so disrupting the break-down of acetylcholine) be used as Alzheimer treatment
cholinergic neuron dies in brain, but enhancing remaining cholinergic neuron signalling through extending lifespan alleviates some earlier symptoms
how can nicotine, muscarine, or neonicotinoid pesticides work to activate acetylcholine receptors
overactivate Ach receptors and overexcites insect nervous system
how can nicotinic toxins block acetylcholine receptors eg: a-bungarotoxin
South-American poison arrow dart, reversible, affects nicotinic receptors
how can atropine be used as an antidote of nerve gas (muscarinic, impacting acetylcholine)
dilates pupil, increase HR by ACh being used by autonomic nerve
antagonist for muscarinic receptors
what are monoamine synthesised from
amino acids
name 2 types of monoamine
catecholamine
serotonin (5-HT)
what is serotonin synthesised from
tryptophan
explain structure of catecholamines, and what they also create
functional group “catechol”, part of biological pathway
precursor = tyrosine
create NTs dopamine, norepinepherine, epinepherine
where are catecholaminergic neurons found
regions of nervous system involved in regulation of movement, mood, attentions, visceral function
explain rate-limiting steps of catecholamine synthesis
enzyme TH catalyses first step in catecholamine synthesis, so is also rate-limiting
TH activities regualted by signals in axon terminal cytosol = causing end-product inhibition
to make more dopamine, add more L-dopa
how are monoamines stored
packaged into vesicle by VMAT (vesicular monoamine transporter)
how are monoamines metabolised, by what
MAO (monoamine oxidase), COMT (catechol-O-methyltransferase) on postsynaptic cells
are monoamines all metabotropic or ionotropic
metabotropic receptors/GPCRs
