SAR At Adrenoreceptors Flashcards
(38 cards)
What is the synapse bridging a neuron and a muscle?
A neuromuscular junction
Broad term is ‘neuroeffector junction’
What’s the benefit of ACh being synthesised in the neuron?
Rapid response
What combines to form ACh?
Acetyl CoA and choline
What enzyme catalyses the formation of ACh?
Choline acetyl transferase
What’s the benefit of ACh being packaged in vesicles?
Protects ACh from degradation
What’s the mechanism of releasing ACh?
ACh is stored into vesicles
Action potential releases ACh
ACh acts on nicotinic receptors - opening ion channel and causing a response
2 ACh molecules are required at nicotinic receptors for a response
How is ACh action terminated? What happens?
Acetylcholine esterase enzyme breaks ACh down into acetic acid and choline, ceasing a response
This is done rapidly, 10,000s of ACh broken down per second
Choline is reclaimed by nerve ending through a choline carrier protein - rate limiting step in ACh synthesis
What drugs interfere with processing of ACh? How do they work?
Vesamicol - blocks transfer of ACh into vesicles
Botulinum toxin - blocks release of ACh from nerve endings
Anticholinesterases - prevents hydrolysis of ACh by AChE in synapse
Hemicholinium - blocks reuptake of choline by NMJ
What is the synthesis of noradrenaline?
Tyrosine is SM
Tyrosine converted to DOPA by tyrosine hydroxylase
DOPA converted to Dopamine by Dopa decarboxylase
Dopamine converted to noradrenaline by Dopamine ß hydroxylase
Where does noradrenaline synthesis occur and what is RDS?
Occurs in noradrenergic nerves
Tyrosine hydroxylase is RDS
How is NA stored?
NA is co-packaged with ATP into vesicles - co-transmission
What is the process of NA release?
Ca2+ enters nerve ending which activates exocytosis of NA from storage vesicles
NA is released and acts on alpha or ß receptor on post-synaptic membrane
It also acts on alpha2 on pre-synaptic nerve which inhibits cAMP production, which inhibits Ca2+ ion channel uptake into nerve ending
It is a negative feedback loop, inhibition of transmitter release.
What is the negative feedback loop of NA release described as?
Autoinhibitory feedback mechanism
What drugs affect the release mechanism of NA?
Disulfuram - inhibits dopamine hydroxylase, hence inhibiting NA synthesis. Mainly used for its action of alcohol, causing worse hangovers
Reserpine - blocks mechanism that transports NA into vesicles
Tyramine/amphetamine - increase release of NA from vesicles
Nimodipine - reduces release by blockade of Ca2+ channels in nerve terminals
Any alpha2 adrenoreceptor-agonist
What are the different subtypes of the adrenoreceptors?
Alpha1 and alpha2
ß1, ß2, ß3
Different subtypes can mediate similar or different responses
Where are alpha1 adrenoreceptors found?
Blood vessels
Gut smooth muscle
Uterus
Liver
Where are alpha2 adrenoreceptors found?
Blood vessels
Gut smooth muscle
Where are ß1 adrenoreceptors found?
Heart - betablockers
Where are ß2 adrenoreceptors found?
Blood vessels
Lungs
Gut smooth muscle
Uterus
Kidney
Liver
What’re the main effects of alpha1 adrenoreceptors?
Contraction of smooth muscle - relaxation in gut
Salivary secretion
Hepatic glycogenysis
What’re the main effects of alpha2 adrenoreceptors?
Inhibition of transmitter release
Platelet aggregation
Contraction of vascular smooth muscle
Decreases insulin release
What’re the main effects of ß1 adrenoreceptors?
Cardiac rate and force
What’re the main effects of ß2 adrenoreceptors?
Bronchodilation
Vasodilation
Relaxation of gut smooth muscle
Hepatic glycogenolyis
Muscle tremor
What’re the main effects of ß3 adrenoreceptors?
Lipolysis - lipid breakdown
