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Where is acetylcholine released in the nervous sytem?

Parasympathetic nervous systema) Pre ganglionic neuronesb) Post ganglionic neuronesSympathetic Nervous Systema) Pre ganglion neuronesb) Some post ganglionic neurones (sweat, ejaculation)


What is acetylcholine synthesized from and how?

Choline and Acetyl Co-A, via the action of choline acetyltranferase.


Where does acetylcholine synthesis take place? What enzyme is produced and how does it get to the nerve terminals?

Acetycholine synthesized in cholnergic neurones.Choline acetyltransferase made in cell bodies of cholinergic neurones.. Transferred to the nerve terminal by axoplasmic transport.


How is acetylcholine packaged for release?

Acetylcholine packed into vesicles and travels to the nerve endings via anteretrograde (movement away from cell body) axoplasmic transport. Stored at nerve ending until action potential arrives.


What is the vesicular ACh transporter?

Carrier protein on surface of vesicle in which ACh is absorbed. Actively transport one molecule ACh into vesicle in exchange for two cytoplasmic protons. Example of antiport.


How is ACh released from axon terminal?

- Action potential arrives- Depolarisation causes voltage gates Ca2+ channels to open- Calcium ions diffuse through down their concentration gradient- Ca2+ binds to synaptotagmin - a membrane trafficking protein- Vesicle brought close to membrane- Snare complex makes a fusion pore- Transmitter released through pore


Give an example of an agent which interferes with ACh release

Botulinum toxin- Taken into neurones by endocytosis- Has protease activity, cleaves SNARE complex and prevents neurosecretory vesicle from fusing with nerve synapse.


How is acetylcholine degraded?

Acetylcholinesterase Abundant enzyme which converts acetylcholine into the inactive metabolies choline and acetate


What happens to the free Choline and Acetate in the synapse?

Choline - transported back into the neurone by a high affinity choline transporter on the membraneAcetate- Converted into acetyle CoA and reused to make ACh by choline acetyltransferase


List some of the important sites of parasympathetic innervation

Innervation of the heartBronchiolesVasculaturePupil of the eyeEndocrine glands


Wjhat is the effect of increased parasympathetic discharge in the heart?

Decrease heart rate (AVN conduction velocity),


Apart from in the parasympathetic system, where else is acetylcholine used in the body?

Preganglioncic in the sympathetic nervouse systemPostganglionic in some part of the sympathetic nervous system, notable to sweat glands (M3)


What are two types of acetylcholine receptors?

Nicotinic and mucarinic


Why are the two types of acetycholine receptors distinguishable?

Muscarinic receptors more sensitive to muscarineNicotinic more responsive to... that's right, you guessed it! Heroin.Lol, JK. Nicotine.


How do nicotinic acetylcholine receptors cause a post ganglionic response?

- Ligand gated ion channel - Channel permeable to Na+ and K+, causes depolarisation (local, immediate)- Action potential propagatesNicotIONe


How do muscarinic acetylcholine receptors cause a post ganglionic response?

- G-protein coupled receptor- G-protein diffuse to membrane protein- Cascade reaction- Signal propagated to whole of cell- Slow response


What is the class of acetylcholine receptor found at the neuroeffector junction?



For the following sub type, give the G protein, the effector and whether it is activatory or inhibitoryM1

GqPhospholipase C activation, creating IP3 that binds to IP3 receptor


For the following sub type, give the G protein, the effector and whether it is activatory or inhibitoryM2

GiInhibits adenylyl cyclaseOpens potassium channels (decreased firing rate action potentials)Inhibitory


For the following sub type, give the G protein, the effector and whether it is activatory or inhibitoryM3

GqActivates phospholipase C, creating IP3 that binds to IP3 receptor


What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological actionSA node

M2Decreased HR


What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological actionBronchi

M3Increased bronchoconstriction


What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological actionBladder

M2 & M3 Contraction causing emptying of the bladder


What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological actionGlands

M3Increased exocrine and endocrine secretions due to contraction of smooth muscle


Parasympathtic nerve terminals at neuroeffector junctions

Acts as a negative feedback mechanism to prevent further ACh release from post synaptic vesicles when ACh conc increases in synapse


What is a cholinoceptor agonist?q

Agent which mimics some or all of the actions of acetycholine


What is the advantage of synthesizing a cholinoceptor agonist which oly interacts with a particular receptor subtype?

Targeted response can be stimulated


What two types of cholinoceptor agonists are available?

Direct = Acts as an analogue to stimulate receptors directlyIndirect - Inhibits acetycholinesterase This prevents the breakdown of Ach and therefore prolongs its activity


Give an example of a clinical use of cholinoceptor agonist

Acelidine - M3 agonistUsed in the treatment of glaucoma, by decreasing intraocular pressure


What is a cholinoceptor antagonist?

Reduce effects of ACh, can act directly or indirectly with varying levels of selectivity


Give an example of Cholinoceptor antagonist and its effects on GI

DicyclomineSyptomatic relief of IBS, reduces small bowel symptomsM1 antagonist


Why are there so many side effects associated with cholinoceptor antagonists?

Control of CNS involves all muscarinic receptors, therefore use of antagonists associated with many side effects


How can cholinoceptor antagonists be used as premedication for anasthesia?

Atropine - Reduces respiratory secretion, therefore minimies risk of aspiration


What effects does the parasympathetic nervous system have on the eye?

Causes- Constriction of pupil- Contraction of cillary muscle to the lens, allowing for closer vision


What effects does the sympathetic nervous system have on the eye?

- Dilates pupil- Relaxes ciliary muscle, allowing more light to enter the eye and far vision


What is glaucoma?

Increase in intraocular pressure due to accumulation of fluid


What effect does pupil dilation have on glaucoma formation?

Impedes drainage of fluid (humour) by blocking the canal of Schlemm


What is the most likely cause of glaucoma?

DiabetesRaised glucose levels = raised osmosis = increase in intraoccular fluid = compression of optic nerve


What are the consequences of increase parasympathetic tone in the eye?

Beneficial to glaucoma- Increases constriction of pupil- Causes canal of schlemm to be unblocked- Allows the drainage of extra fluid


Which receptor ligands are used to clinically treat glaucoma?

- The sphincter muscle in the eye has M3 muscarinic receptors- Muscarinic agonists will activate contriction of spincter muscles, unblocking drainage path.


Givethree non-receptor treatments are used for glaucoma?

Protaglandin analogue - increases uveoscleral outflowCarbonic anhydrase inhibitor - decrease aqueous formation by the cillary bodyTopical symathomimetics - reduce intraocular pressure by decreasing aqueous production and increasing aqueous drainage


What would be the effects of increasing sympathetic tone of the eye?

Dilate the pupilCausing raised intraocular pressure


What agents, active at adrenoceptos, are used clinically in the treatment of glaucoma

Beta blockers - slow down production of aqueous humour Clonidine - alpha 2- adrenergic agonist - increases uveoscleral outflow