Cholinergic

Question 1

Describe the synthesis, release and breakdown of acetylcholine.

Answer 1

Acetylcholine is made in the nerve terminal from acetyl coA and choline by choline acetyl transferase. It is then packaged into vesicles. When the action potential comes it opens voltage sensitive calcium channels, the inrush of calcium hopshorylates snare proteins e.g. synaptobrevin located on the vesicle - this causes them to dock with the snare proteins anchoered to the presynaptic membrane e.g.SNAP-25 and syntaxin - this cases exocytosis of acetylcholine from the vesicle where it then goes on to have a number of effects on the receptors on the post synaptic membrane. Acetlycholine is broken down in the synaptic cleft by acetylcholinesterase, or in the plasma but more unspecific butrylylesterases , into choline and acetate. The choline is then reuptaken into the nerve terminal to be used to make new acetylcholine.

Question 2

Streptomycin

Answer 2

Blocks calcium channels on the presynaptic elements and prevents release of acetylcholine

Question 3

Botlinum toxin

Answer 3

An extreme potent compound - comprised of heavy and light chain subunits - when it is taken up into the nerve terminal it is cleaved and the light chain subunits have pepsidase activity and destroy SNARE proteins - when synaptobrevin on the vesicle is destroyed this means that the vesicle cannot dock and acetylcholine cannot be released causing muscle paralysis.

Question 4

Vesamicol

Answer 4

Blocks acetylcholine uptake into vesicles

Question 5

Hemicholnium-3

Answer 5

Inhibits choline reuptake

Question 6

Trymethylcholine

Answer 6

Similar structure to choline so is taken up into the nerve terminal by the choline transporter where it is synthesised and released but does not have any of the actions of acetylcholine

Question 7

Describe the action of acetylcholine on the heart.

Answer 7

Acetylcholine is released from the parasympathetic nervous system by the vagus nerve to the heart where it binds to m2 receptors in the heart, m2 receptors are coupled to gi which leads to a decreassed in cAMP and a decreased in PKA. PKA usually does the whole thing with MLCK and therefore inhibiting this leads to reduced contraction and therefore reduced heart rate. The m2 receptors are abudant in nodel and sino atrial tissues and acetylcholine causes decreased AV conduction which leads to the slowing of the heart. The gi protein is also coupled to a potassium channel which increasing the hypoerpolarisation of the cardiac myocytes preventing contraction.

Question 8

Describe the action of acetylcholine on the blood vessels

Answer 8

There is no direct parasympathetic innervation of blood vessles however the acetylcholine that is released binds to m3 receptors on the endothelial cells on the blood vessels. m3 receptors are coupled to gq which is blah blah leads to the increase in calcium which activates NO synathase and converts L-arginine to NO which leads tothe exocytosis of NO which then binds to soluble guanlylate cylase and causes release cGMP > PKG which then acts to reduce intraceullar calcium via a variety of mechanisms so this causes vasodilation of the blood vessels

Question 9

Describe the effects of acetylcholine on the glands

Answer 9

Normally the sympathetic division has a short pregangionc fibre that releases ach at ganglia and the post ganglionc fibre then goes on to release NA and act to prroduce those effects. An exception is made by symathetic innervation of the sweat glands wehrre by one fibre from the sympathetic division releases ach. It acts on m3 receptors on secretory cells in the sweat glands, salivary glands, lacrimal glands and pancreas (m3 on b cells leads to insulin secretion).

Question 10

Describe the effects of acetylcholine in the eye

Answer 10

There are two muscles in the eye involved in opening and closing the iris to contract and dilate the pupil. The dilator pupilae causes myadrias and is activated by Na acting on a1 receptors. The contractor pupillae pulls the iris closed and is activated by acetylcholine on the m3 muscarninic receptors and this leads to miosis.

Question 11

Describe the effects of acetylcholine in the gut.

Answer 11

Binds to musarnic receptors to stimulate contraction of the gut ans also seretion of gastric acid

Question 12

Describe the effects of acetylcholine on bronchial smooth muscle

Answer 12

Binds to m3 receptors and ccauses constriction of the bronchial smooth muscle

Question 13

Atropine

Answer 13

Muscarnic receptor antagonist used to inhibit gut motility

Question 14

Tropicamide

Answer 14

M3 muscarnic receptor antagonist used in eye examinations

Question 15

Cyclopentone

Answer 15

Long lasting eye procedure m3 muscarnic antagonist

Question 16

Propantheline

Answer 16

Injectable muscarnic aantagonist blocks m3 to treat sweat secretions in hyperhydrosis

Question 17

Hyoscince

Answer 17

Anticholinergic used to dry up secretions in surgery

Question 18

Pirenzipine

Answer 18

Blocks muscarnic activated secretions of gastric acid used in peptic ulcers

Question 19

Ipatropium

Answer 19

M3 muscarnic receptor block in bronchial smooth muscle used to treat asthma but has a variaty of side effects that mean they are not he most popular

Question 20

Describe how glaucoma could be treated with muscarninc agonist?

Answer 20

Muscarninc agonists like pilocarpine andcarbachol could be used to treat glaucoma. In glaucoma there is a build up of fluid in the canal of schwemm this leads to an increase in intraoccular pressure which can lead to blindness. By activaing the contractor pupillae via m3 receptors this would pull the canal open and relieve the pressure

Question 21

Echothiopate

Answer 21

Used as eye drops to block cholinesterases to increase activity of acetylcholine on m3 receptors on the contractor pupillae muscle to relief symptoms of glaucoma

Question 22

Neostigmine

Answer 22

Treat myasthias gravis

Question 23

Dyflos

Answer 23

Irreverisible inhibition of acetylcholine esterase reversed with pralidoxime