Block B Lecture 1 - Classification and Structure of Adrenoceptors

Question 1

What are 5 things which the sympathetic nervous system does in response to the threat of trauma?

Answer 1

Answers Include:
Dilates Pupils
Increases heart rate
Opens airways
Slows digestive system
Increases blood flow to the brain and skeletal and cardiac muscle
Constricts peripheral blood vessels
Increases breathing speed
Increases sweat production
Decreases saliva production
Inhibits voiding
(Slide 6)

Question 2

What neurotransmitter does the sympathetic nervous system use in preganglionic neurons?

Answer 2

Acetylcholine
(Slide 8)

Question 3

What are 4 neurotransmitters that the sympathetic nervous system uses post ganglionic neurons?

Answer 3

Acetylcholine, Noradrenaline, Adrenaline and Dopamine.
(Slide 8)

Question 4

What occurs in the adrenergic pathway of the sympathetic nervous system?

Answer 4

Acetylcholine is released from preganglionic neurons which binds to nicotinic receptors located on the surface of postganglionic neurons, triggering noradrenaline release from postsynaptic neurons. Noradrenaline then binds to α or β adrenoceptors in the heart or blood vessels, with effects varying via subclasses
(Slide 8)

Question 5

What happens in the cholinergic pathway of the sympathetic nervous system?

Answer 5

Acetylcholine is released from preganglionic neurons which binds to nicotinic receptors located on the surface of postganglionic neurons, triggering acetylcholine release. Acetylcholine then binds to muscarinic receptors in the sweat gland, resulting in increased sweat production
(Slide 8)

Question 6

What happens in the dopaminergic pathway of the sympathetic nervous system?

Answer 6

Acetylcholine is released from preganglionic neurons which binds to nicotinic receptors located on the surface of postganglionic neurons, triggering dopamine release. Dopamine then binds to dopamine receptors in renal blood vessels, triggering vasodilation, resulting in increased renal blood flow.
(Slide 8)

Question 7

List all of the classes and subtypes of adrenoceptors.

Answer 7

α1-adrenoceptors - 3 subtypes: α1A, α1B and α1D
α2-adrenoceptors - 3 subtypes: α2A, α2B and α2C
β-adrenoceptors - 3 subtypes: β1, β2 and β3
(Slide 10)

Question 8

What was the first hormone to be discovered, and who discovered it?

Answer 8

Adrenaline was the first hormone to be discovered, and it was discovered by physician George Oliver
(Slide 11)

Question 9

What did George Oliver’s experiment in 1895 tell us?

Answer 9

That extract from the adrenal gland (which was later identified as adrenaline) evoked vasoconstriction in peripheral blood vessels and increased heart rate (in sheep and cats)
(Slide 12)

Question 10

What experiment did Dale do in 1905 that prove that there were multiple types of adrenoceptors?

Answer 10

He did a control experiment, which resulted in adrenaline increasing blood pressure. In a different group, he added an ergotoxine treatment, resulting in adrenaline decreasing blood pressure
(Slide 13)

Question 11

How did Ahlquist use pharmacology principles to prove the existence of 2 adrenoceptor types?

Answer 11

He used the rank of agonist potency.

E.g Alpha adrenoceptors:
noradrenaline > adrenaline&raquo_space; isoprenaline
Beta adrenoceptors
isoprenaline > adrenaline > noradrenaline
Different rank of agonist potency means different receptor types / subtypes
(Slide 15)

Question 12

Where were β3 receptors identified?

Answer 12

Adipose tissue
(Slide 17)

Question 13

What 3 methods led to the current classification of adrenoceptors?

Answer 13

Radioligand binding
Selective pharmacology
Molecular cloning
(Slide 20)

Question 14

What is the basic structure of an adrenoceptor?

Answer 14

G-protein coupled receptors, 7 transmembrane domains and 3 extracellular loops and has an amino terminus, 3 intracellular loops and carboxyl terminus
(Slide 24)

Question 15

What does changing the amino acid structure of a receptor allow?

Answer 15

Mapping of interactions
(Slide 26)

Question 16

What is the difference between a neurotransmitter and a hormone?

Answer 16

Neurotransmitters are synthesised by neurons and hormones are synthesised by the adrenal gland
(Slide 27)

Question 17

What are catecholamines?

Answer 17

A group of neurotransmitters which are derived from the amino acid tyrosine and play crucial roles in the nervous system and the endocrine system
(Slide 27)

Question 18

What 3 neurotransmitters make up the catecholamine group?

Answer 18

Dopamine
Noradrenaline (Norepinephrine)
Adrenaline (Epinephrine)
(Slide 27)

Question 19

How are the 3 catecholamines synthesised?

Answer 19

1. Tyrosine hydroxylase adds a hydroxyl (-OH) group onto L-tyrosine to form L-DOPA
2. DOPA decarboxylase removes the carboxyl (-COOH) group from L-DOPA to form dopamine
3. Dopamine β-hydroxylase adds a hydroxyl group onto the β carbon (the one next to the one the amine group is attached to) forming Noradrenaline
4. Phenylethanolamine N-methyltransferase (PNMT) adds a methyl group to to the amine group of noradrenaline, forming adrenaline

(Slide 27)

Question 20

What is β-hydroxyl essential for and why?

Answer 20

Adrenoceptor activation - (as dopamine has very little activity) addition of a methyl group converts NA to adrenaline and changes its activity
(Slide 28)

Question 21

What is isoprenaline?

Answer 21

An isopropyl amine analogue of adrenaline, with a bulkier isopropyl group attached to the nitrogen (2nd degree amine)
(Slide 29)

Question 22

What differs in isoprenalines adrenoceptor activity compared to noradrenaline and adrenaline?

Answer 22

It loses its α-adrenoceptor activity and enhanced β-αadrenoceptor
(Slide 29)

Question 23

What is dichloroisoprenaline?

Answer 23

Its an isoprenaline analogue where the hydroxyl groups are replaced by chlorine atoms
(Slide 30)

Question 24

How does dichloroisoprenaline adrenoceptor activity differ from isoprenaline activity?

Answer 24

It antagonists β-adrenoceptor activity
(Slide 30)