The sympathetic nervous system

Question 1

What is the structure of Acetylcholine, label the charges if there are any present?

Answer 1

Question 2

What are the substrates of Acetylcholine?

Answer 2

The substrates are Choline and AcetylCoA

Question 3

How is choline taken up into the nerve terminal?

Answer 3

By a choline transporter in the membrane, this is the rate limiting step for synthesis

Question 4

What is the reaction for the production of Acetylcholine?

Whats the by product?

What enzyme is used?

Answer 4

AcetylCoA + Choline –> Acetylcholine + CoA

Enzyme: Choline Acetyltransferase (CAT)

Question 5

How is Ach taken up in vesicles?

Are these pre or post synaptic vesicles?

What can this process be blocked by?

Answer 5

ACh is taken up into presynaptic Vesicles by an active transport process. This can be blocked by Vesamicol

Question 6

What is ACh released in response to?

Answer 6

ACh is released in response to calcium entry into the presynaptic terminal

Question 7

How is ACh inactivated?

What are the stages to this process?

Answer 7

1. Following release into the synaptic cleft, ACh is available to active receptors
2. The synaptic cleft is also rich in the enzyme Acetylcholinesterase which breaks ACh down into choline and acetic acid
3. choline is taken back up into the nerve terminal by the choline transporter. this is blocked by Hemicholinium

Question 8

What 3 compounds did dale use to characterise cholinergic transmission?

Answer 8

• Muscarine
• Nicotine
• Atropine

” two distinct types of action can be detected- a ‘muscarine’ action, paralysed by atropine, and a ‘nicotine’ action, paralysed by excess of nicotine”

Question 9

What did Dale’s experiment show using ACh?

Answer 9

• It produces 2 different effects on blood pressure
• Why does the same compound triggers two dose-dependent opposite responses?
• Shows muscarinic and nicotinic receptors

Question 10

Draw the parasympathetic organ synapse

Answer 10

Question 11

Draw the structure of Muscarine

Answer 11

Question 12

WIth muscarinic transmission, what is the main agonist?

Answer 12

Muscarine

Question 13

Table showing how different drugs effect different chemicals actions

Answer 13

Question 14

Tell me the effects that the agonists have on the below organ system when they bind to muscarinic receptors?

• Cardiovascular system
• Gastrointestinal actions
• Exocrine gland secretion

Answer 14

• Cardiovascular decreases HR, CO and vasodilation
• Gastrointestinal actions increased activity (GIT smooth muscle contracts and increased peristaltic activity)
• Exocrine gland secretion increased sweating, lacrimation and salivation (contracts bladder and bronchial smooth muscles; sweating, lacrimation, salivation, bronchial secretion)

Question 15

Why does a decrease in HR and CO result in a sharp fall in BP?

Answer 15

mAChR result in release of NO which causes vasodilation

Question 16

What is the treatment of acute angle-closure Glaucoma?

Answer 16

• parasympathetic innervation of constrictor pupillae
• parasympathetic innervation of ciliary muscles: use of pilocarpine in glaucoma to relieve pressure
• contracts ciliary muscle in the eye- this can help relieve increased intraocular pressure in glaucoma (commonest cause of blindness). (pilocarpine can be used)

Question 17

What are the main muscarinic receptor subtypes and what type of receptors are they?

Answer 17

M1: Neural

M2: Cardiac

M3: Glandular

They are all G protein coupled receptors (GPCRs)

Question 18

Tell me the following about the M1 receptor…

• Main location
• Cellular action
• Function

Answer 18

Question 19

Tell me the following about M2 receptors…

Main location

Cellular action

Function

Answer 19

Question 20

Tell me the following about M3 receptors

Main location

Cellular action

Function

Answer 20

Question 21

What muscarinic receptors are stimulatory and which are inhibitory?

Answer 21

Stimulatory: M1, M3, M5

Inhibitory: M2 and M4

Question 22

Muscarinic

Answer 22

Question 23

Name the muscarinic receptor antagonists?

Answer 23

Atropine

Pirenzepine

Question 24

What are the effects of muscarinic antagonists?

Answer 24

• inhibition of secretions
• effect on heart rate
• effects on the eye
• effects on the gut
• effects on other smooth muscle
• effects on the CNS
• CLINICAL USES

Question 25

What are the receptors for ACh in the sympathetic and parasympathetic nervous system?

Answer 25

Muscarinic is the receptor in the parasympathetic nervous system Nicotinic is the receptor in the sympathetic nervous system

Question 26

What enzyme is used to break down the neurotransmitter ACh?

Answer 26

Acetylcholinesterase

Question 27

Draw and explain nicotinic transmission at autonimic ganglia

Answer 27

Question 28

What type of channels are nicotinic receptors and what are they permeable to?

Answer 28

All nicotinic receptors are **ligand-gated ion channels** are are permeable to cations

Question 29

Whats different with the nicotinic receptors compared to those from the muscle?

Answer 29

The isoform at the ganglia is different from the muscle

Question 30

When ACh binds to the nicotinic receptor, what movement of ions occurs?

Answer 30

Na+ are imported and K+ exported

Question 31

Tell me the structure of the ligand-gated ion channels

Answer 31

* 5 subunits * 2x alpha, 1x beta, 1x delta and 1x gamma * alpha subunits contain the binding sites for ACh * When Ach binds to binding sites in alpha subunits, the ion channel opens, and changes permeability and drives change In current in post synaptic axon

Question 32

What are the types of nicotinic receptors and where are they found?

Answer 32

* N2 is also called N_N as it is based at neurons * N₁ is also called N_M as it is found at neuromuscular junctions

Question 33

Name some nicotinic receptor agonists

Answer 33

* Acetylcholine * Nicotine * Dimethylphenylpiperazimium (DMPP)

Question 34

Identify the structures of each of these nicotinic receptor agonists

Answer 34

Question 35

What are the effects of nicotine and DMPP ?

Answer 35

**Nicotine:** stimulation of autonomic ganglia **EMPP:** stimulation of autonomic ganglia. DMPP is a non-natural drug used to agonise nicotinic receptors

Question 36

Name a nicotinic ganglionic recetor antagonist

Answer 36

Question 37

What compound blocks ganglionic nicotinic receptors

Answer 37

Hexamethonium

Question 38

What is the cat nictitating membrane?

Answer 38

A third eyelid (the sideways eyelid). Cats have 2 sets of eyelids, the ones that go up and down and always a sideways eyelid. This protects from night vision and to keep the eye moist all the time to help with night hunting and general eye function

Question 39

What does this experiment tell you about the action of hexamethonium?

Answer 39

* Took a cat, study both left and right eye at the same time * Look at one eye for stimulation of preganglionic site e.g. left eye * Postganglionic neuron Is removed for superior cervical ganglion in the other eye e.g. right eye * Dots indicate electrical stimulation * Top shows recording of blood pressure so can study the physiological consequences * Stimulate pre and post ganglionic sites and get contraction of nictitating membrane and drop in BP * Apply nicotine instead, sees drop in preganglionic neuron, but still contraction * Post doesn’t have ganglion has been removed so no contraction seen there * Apply adrenaline, directly stimulating membrane. Therefore, doesn’t matter if preparation is intact (with ganglion) or not as still causes a contraction * Apply C6, antagonist of nicotinic receptor, try to repeat stimulation with nicotine after. Not seeing same stimulation as before. No longer see any response at pre- therefore indicating there’s something in ganglion that activated by nicotine that’s now blocked by C6. When apply with adrenaline still causes response so **shows that C6 was a nicotinic receptor antagonist**

Question 40

Whats are the pharmacological actions of hexamethonium?

Answer 40

* Blocks the nicotinic receptor- no agonist action * Reduces blood pressure (beneficial for hypertension) * Dry mouth * reduced gastric acid secretion * Constipation * Urinary retention * Blurred vision * Postural Hypotension * Sexual dysfunction

Question 41

Whats series of compounds does Hexamethonium belong to? How are they named?

Answer 41

Belongs to a series of compounds known as **polymethylene bismethonium** They're names depending on the number of carbons in their chain

Question 42

What experiment did Paton and Zaimis do with polymethonium?

Answer 42

* Paton and Zaimis compared the effect of polybismethonium compounds at autonomic ganglia and neuromuscular junction * Balance of affinity and potency for good pharmacological agents