Acetylcholine Flashcards
Where in the parasympathetic nervous system is acetylcholine found?
In both pre and postganglionic synapses
Where in the sympathetic nervous system is acetylcholine found?
In preganglionic fibres and at neuroeffector junctions for arrector pili muscles and thermoregulatory sweat glands.
What are the precursors for acetylcholine and what enzyme converts them to it?
Acetate and choline.
Choline acetyl transferase (ChAT)
Where in a neuron is acetylcholine produced?
Presynaptic bulb
Where do the precursors for acetylcholine come from?
Acetate from acetyl~CoA
Choline taken up by CHT closer to the synapse
How is acetylcholine packaged into vesicles?
V-AChT
Describe the regulation of acetylcholine release.
Synaptotagmin is bound to the vesicle and attaches to a SNARE complex (VAMPs and SNAPs).
When calcium ions enter the bulb it causes the complex to open and form a fusion pore.
Describe one substance which prevents the release of acetylcholine.
Botulism toxin - cleaves the SNARE proteins to prevent the complex from forming
k-neurotoxin - stops the fusion pore opening
Describe how acetylcholine action is terminated
Acetylcholinesterase breaks down ACh in the synapse.
What drugs prevent the termination of acetylcholine action and what can they be used for?
Neostigmine/pyridostigmine
Reverse neuromuscular block or treat myasthenia gravis
Describe the fate of the products of acetylcholine breakdown
Free choline taken up by a high affinity choline uptake system and is only used to make ACh.
Acetate disperses freely into the surrounding tissues and can be used to make acetyl~CoA
What type of receptors are nicotinic cholinoceptors?
Ligand gated ion channels which are permeable to both sodium and potassium
What type of receptor are muscarinic cholinoceptors?
G-protein coupled receptors.
Give the four subtypes of muscarinic cholinoceptors and their action.
M1 - Gq - activate phospholipase C
M2 - Gi - inhibit adenylyl cyclase
M3 - Gq - activate phospholipase C
M4 - Gi - inhibit adenylyl cyclase
What type of muscarinic cholinoceptor is found in the SAN and what action does it have?
M2
Decreases cAMP which reduces HCN channel activation and therefore decreases heart rate
What type of muscarinic cholinoceptor is found in the bronchi and what action does it have?
M3
Increases intracellular calcium which increases contraction
What type of muscarinic cholinoceptor is found in the bladder and what action does it have?
M3
Dilates the bladder by reducing smooth muscle contraction
What type of muscarinic cholinoceptor is found in exocrine glands and what action does it have?
M1
Increases function by increasing cAMP
What type of muscarinic cholinoceptor is found in salivary glands and what action does it have?
M3
Increases calcium and fluid secretion
What type of muscarinic cholinoceptor is found in PNS terminals and what action does it have?
M1
Decreases potassium conductance
What is the advantage of synthesising cholinoceptor agonists which are specific for a receptor subtype?
Decreases the number and severity of side effects.
Give the effect of parasympathetic action on one area of the eye.
Contract sphincter pupillae which constricts the pupil
Contracts ciliary muscle which focusses the eye for near vision
Enhance drainage of aqueous humour through the trabecular meshwork or canal of Schlemm
Give the effect of sympathetic action on one area of the eye.
Contracts dilator pupillae which dilates the pupil
Contracts the superior tarsal muscle in the eyelid to help to hold it open.
Enhances aqueous humour formation (beta-2)
Inhibits aqueous humour formation (alpha-1)
Relaxes ciliary muscle for distant vision
Describe what causes glaucoma.
Reduced ability to drain fluid out of the eye due to blocked trabecular meshwork.
Can be caused by diabetic retinopathy, prolonged steroid use and trauma.
Describe a treatment for glaucoma.
Pilocarpine which activates M3 receptors
Alpha adrenergic agonists which decreases production of aqueous humour by ciliary bodies and increases uveoscleral flow
Prostaglandin analogues as the receptors increase outflow of fluid
Beta adrenergic antagonists which decrease aqueous humour production
Acetylcholinesterase inhibitors which decrease the breakdown of ACh so increase the stimulation of muscarinic receptors
Brimodine which inhibits adenylyl cyclase, reducing cAMP production and causing vasoconstriction. Decreases aqueous humour production and increases uveoscleral outflow
