Adrenergic and Cholinergic Receptors

Question 1

What are adrenergic receptors?

Answer 1

G-protein coupled receptors that bind adrenaline and noradrenaline, mediating the sympathetic nervous system

Question 2

What are cholinergic receptors?

Answer 2

Ligand-gated ion channels or G-protein coupled receptors that bind acetylcholine

Question 3

What are Muscarinic receptors and where do they function?

Answer 3

G-protein coupled receptors that function in the CNS and PNS, as part of the parasympathetic nervous system.

Question 4

What are Nicotinic receptors and where do they function?

Answer 4

Ionotropic ligand-gated ion channels that function in the CNS (post-synaptic autonomic ganglia) and post-synaptic neuromuscular junctions, as part of the sympathetic and somatic nervous systems.

Question 5

What are alpha1 adrenergic receptors?

Answer 5

Found in vascular smooth muscle cells, they mediate intracellular calcium concentration and muscle contraction

Question 6

What are alpha2 adrenergic receptors?

Answer 6

Found in presynaptic neurons, they mediate calcium ion concentration and secretion of noradrenaline

Question 7

What are beta1 adrenergic receptors?

Answer 7

Found in cardiac muscle, they mediate heartrate and force

Question 8

What are beta2 adrenergic receptors?

Answer 8

Found in airway smooth muscle cells, mediate dilation

Question 9

What are beta3 adrenergic receptors?

Answer 9

Found in adipose tissue, they mediate lipolysis

Question 10

Describe a general adrenergic receptor agonist

Answer 10

Used for cardiac arrest or anaphylactic reactions, or taken with local anaesthetic to prolong activity. This is because adrenaline has a short duration of action and is non-selective

Question 11

Describe an alpha1 antagonist

Answer 11

Used for treating hypertension

Question 11

Describe an alpha1 agonist

Answer 11

Used for treating nasal congestion and hypotension. Most of these drugs have a lack of the para OH group to prevent beta activity, and a smaller substituent on the amine which allows binding in alpha receptors

Question 12

Describe an alpha2 agonist

Answer 12

Act centrally (CNS) to decrease sympathetic flow of adrenaline and noradrenaline from the brain, treating hypertension

Question 13

Describe a beta1 agonist

Answer 13

Used for cardiac shock treatment, short acting as it is easily metabolised due to catechol ring and phenol, the large R group makes it beta-selective, and the extra OH group in the phenol causes hydrogen bonding with the extra polar binding region

Question 14

Describe a beta2 agonist

Answer 14

SABAs: e.g. salbutamol, used to treat asthma attacks. Drugs can be non-selective or beta- or beta2-selective

LABAs: hydrocarbon substituent causes it to be longer acting

Question 15

Describe a beta1 antagonist

Answer 15

Beta blockers, used to treat angina and hypertension ??

Question 16

What are direct, indirect and mixed acting drugs?

Answer 16

Direct - Drugs that target the receptor
Indirect - drugs that regulate neurotransmitter release, synthesis, breakdown, uptake, storage or release
Mixed - act directly and indirectly

Question 17

Give an example of a mixed acting drug

Answer 17

Ephedrine and psuedoephedrine directly activate alpha and beta receptors, and indirectly act by inhibiting noradrenaline reuptake and increasing noradrenaline release from vesicles in nerve cells

Question 18

What makes acetylcholine a flexible molecule

Answer 18

It can adopt different conformations allowing it to bind to both muscarinic and nicotinic receptors

Question 19

Describe muscarinic antagonists

Answer 19

Cause increased heart rate, relaxation of smooth muscles, inhibition of gastric acid and saliva secretion

Question 20

Describe drugs that act on nicotinic receptors

Answer 20

depolarising blockers - agonist?? produces initial contraction of muscle fibres. Prevents end-plate potential from producing a propagated action potential by maintaining depolarisation

Non-depolarising blocker - competitive antagonist, competes against acetylcholine to block transmission

Question 21

Describe Anticholinesterase

Answer 21

inhibits acetylcholinesterases to slow/prevent degradation of acetylcholine released at synapses.

Short acting - bind to anionic site of cholinesterase
Medium acting - interact with the serine hydroxyl of esteractic site, produces carbamylated enzymes which are hydroxylated slower
Long acting - irreversibly phosphorylates serin hydroxyl group of esteractic site. this takes days to regenerate

Question 22

Describe Cholinesterase

Answer 22

Serine hydrolases that catalyse hydrolysis of acetylcholine into choline and acetic acid, the active centre of cholinesterase has 2 areas (anionic and esteractic sites) that both interact with acetyl choline

Question 23

What is the neurotransmission process of noradrenaline?

Answer 23

NA is synthesised in presynaptic neuron and stored.
Activation signal causes fusion of the vesicles and releases NA into the synaptic cleft.
NA binds to receptor on postsynaptic neuron, causing a new signal.
NA departs from receptor back to the presynaptic neuron.
NA is reabsorbed by active transport into the presynaptic neuron and repackaged or metabolised.

This process is inhibited by:
Self-inhibition, high conc of noradrenaline at presynaptic alpha2 receptors.
Prostaglandin acting on prostaglandinE2 receptors.
Acetylcholine acting on presynaptic muscarinic receptors.