Cholinergic Effects

Question 1

List the five muscarinic receptors are where they are found.

Answer 1

M1 - CNS, peripheral neurones, gastric parietal cells
M2 - atria, SAN, AVN
M3 - Visceral smooth muscle, secretory glands, endothelial cells
M4 - CNS
M5 - CNS

Question 2

What is the difference between nicotinic and muscarinic receptors?

Answer 2

They both act as acetylcholine receptors.
Nicotinic receptors are ligand-gated ion channels that mediate a fast synaptic transmission of the neurotransmitter.
Muscarinic receptors are G-protein coupled receptors (GPCRs) that mediate a slow metabolic response via second messenger cascades.

Question 3

List some organs that are part of the parasympathetic body.

Answer 3

• iris (eye)
• lacrimal (tear) gland
• salivary glands
• bronchi (lungs)
• heart
• stomach
• liver
• adrenal glands
• kidney
• intestines
• colon
• bladder
• external sex organs

Question 4

List some of the main parasympathetic effects.

Answer 4

• reduced heart rate
• vasodilation
• increased saliva and gastric acid production
• increased tear formation
• visceral smooth muscle contraction
• pupil constriction

Question 5

We know that muscarinic receptors are G-protein coupled receptors. What αG subunit does each of them have?

Answer 5

The M1,3 and 5 receptors have αGq/11 subunits.

The M2 and 4 have αGi subunits.

Question 6

Describe the cardiac effects that follow the stimulation of the M2 receptor.

Answer 6

When the M2 receptor is stimulated (vagus nerve stimulated), it leads to a decrease in heart rate.
This occurs because the M2 receptor has a αGi subunit, which reduces the amount of cAMP made. This means that less PKA is made, which releases less Ca2+, which leads to decreased contractions.

Question 7

Describe the vascular effects that follow the stimulation of the M3 receptor.

Answer 7

When stimulated, the acetylcholine binds and activates it. The Phospholipase C then activates NO Synthase, which synthesises NO from Arginine.
Since there are no receptors on smooth muscle cells (only endothelial cells), to synthesise NO, it needs to be sent there. There is the rapid diffusion of NO into smooth muscle cells.
There, they bind to guanylyl cyclase, which converts GTP to cGMP. This causes the rapid relaxation of smooth muscle cells.

Question 8

How do the parasympathetic and sympathetic systems affect the eye?

Answer 8

The parasympathetic system causes the contraction of circular muscle via M3 receptors, leading to pupil constriction.
The sympathetic system causes the contraction of radial muscle via α1 receptors, leading to pupil dilation.

Question 9

List some clinical uses of parasympathomimetics.

Answer 9

DIRECTLY ACTING:

• PILOCARPINE (mAChR agonist) is used to treat glaucomas and dry mouth. It’s used in sweat tests. Glaucomas stem from poor drainage of fluid through the trabecular network; this is often due to a dilated iris.
• BETHANECHOL (mAChR agonist) is occasionally used to aid bladder / gastric emptying
• SUCCINYLCHOLINE (high-affinity nAChR agonist) is used in surgery – depolarising paralysis.

INDIRECTLY ACTING

• AChE inhibitors such as TACRINE, DONEPEZIL or RIVASTIGMINE used in dementia
• Neuromuscular diseases such as MYASTHENIA GRAVIS or EATON-LAMBERT syndrome.

Question 10

List some clinical uses of muscarinic blockers.

Answer 10

• Premedication before anaesthesia to reduce secretions, sedation (hyoscine), prevent vagal effects
• In heart block to increase AV conduction
• Ophthalmology to produce mydriasis for examination
• Bronchodilatation in COPD
• Anti-spasmodic in GI colic
• Treatment of antiChE poisoning
• Motion sickness

Question 11

List some clinical uses of nicotinic blockers.

Answer 11

Used as muscle relaxants
Direct nAchR blockers:
- tubocurarine
- pancuronium
- vecuronium
- atracurium

Used as depolarising blockers
Direct nAchR agonists
- suxamethonium