Adrenergic receptors and synapses

Question 1

What molecules synthesise acetylcholine?

Answer 1

Choline + Acetyl coenzyme A
Catalysed by choline acetyltransferase

Question 2

What molecules synthesise Noradrenaline?

Answer 2

Tyrosine + Tyrosine hydroxylase (limiting reagent) —> DOPA

DOPA + DOPA decarboxylase —> Dopamine

Dopamine + Dopamine beta-hydroxylase —> Noradrenaline

Question 3

How does choline and tyrosine enter the synapses?

Answer 3

Na+ transporter (symporter)

Question 4

What receptors does noradrenaline act on?

Answer 4

Adrenergic

Question 5

What receptors does acetylcholine act on?

Answer 5

Muscarinic
Nicotinic

Question 6

What type of receptors are nicotinic?

Answer 6

Ligand gated ion channels

Question 7

What type of receptors are muscarinic?

Answer 7

GPCR

Question 8

Where are adrenergic receptors found?

Answer 8

At the end of the post-ganglionic neuron for the sympathetic nervous system

Question 9

Where are nicotinic receptors found?

Answer 9

At the ganglionic synapse for both the parasympathetic and sympathetic NS

Question 10

Where are muscarinic receptors found?

Answer 10

At the end of the post-ganglionic neuron for the parasympathetic NS

Question 11

Summarise how vMAT works and what its function is

Answer 11

Function = transporting NA into vesicles for transportation

Hydrolysis of ATP = H+ into vesicle
Proton pump = H+ out, NA in

Question 12

What inhibits vMAT?

Answer 12

Reserpine

Question 13

What is the consequence of reserpine?

Answer 13

NA not transported and released
Doesn’t act on adrenergic receptors
Sympathetic affects cant be produced
Decrease HR
Decrease in renin release

Question 14

What causes Ca2+ to be released

Answer 14

Action potential - depolarisation = Ca2+ channels open

Question 15

What type of channels are Ca2+

Answer 15

L-type voltage gated ion channels

Question 16

Where does Ca2+ get released into?

Answer 16

Pre-synaptic terminal

Question 17

What is the consequence of an increase in Ca2+?

Answer 17

Vesicle fusion to membrane and release of neurotransmitter

Question 18

What is the process called for the release of the neurotransmitter?

Answer 18

Exocytosis

Question 19

What drug blocks the release of the neurotransmitter?

Answer 19

Guanethidine

Question 20

What is the enzyme responsible for breaking down acetylcholine in the synaptic clef?

Answer 20

Acetylcholinesterase

Question 21

Why is noradrenaline metabolism important?

Answer 21

Terminates noradrenaline

Question 22

What are the 2 enzymes responsible for metabolising NA?

Answer 22

MAO - monoamine oxidase
COMT - Catechol-O-methyl transferase

Question 23

What does MAO metabolise NA to?

Answer 23

An aldehyde

Question 24

What does COMT metabolise NA to?

Answer 24

Carboxylic acid

Question 25

What cofactor does COMT use?

Answer 25

SAM - S Adenosyl methionine

Question 26

What type of enzyme is COMT?

Answer 26

Mg2+ metalloprotease

Question 27

Why are using MAO or COMT inhibitors not beneficial?

Answer 27

Because noradrenaline has a high percentage of reuptake meaning it can be recycled and the process can happen again

Question 28

What do selective seretonin reuptake inhibitors inhibit?

Answer 28

Inhibit reuptake of 5-HT

Question 29

How do neurotransmitters pass the synaptic clef?

Answer 29

Diffusion

Question 30

What type of receptors are adrenergic receptors?

Answer 30

GPCR

Question 31

What are the 3 adrenergic binding sites and what amino acids do each of them have?

Answer 31

TM3 - aspartic residue TM5 - X2 Serine residue TM6 - Phenylaniline and asparagine

Question 32

What enantiomer must the alcohol group be on a drug for beta 2 agonists?

Answer 32

R- enhances activity

Question 33

What type of amines must the drug have for optimal activity?

Answer 33

Secondary

Question 34

What gives beta selectivity over alpha?

Answer 34

Substituted hydrophobic chain from amine

Question 35

What is the downstream effects of beta2 agonists?

Answer 35

G alpha s Increase cAMP + PKA PKA deactivates MLCK MLCK can phosphorylate myosin no smooth muscle contraction

Question 36

Why is a substitution on the meta carbon important for beta2 agonists?

Answer 36

Stops the metabolism of the drug by COMT - wont become inactivated

Question 37

What must the meta substituent be able to do on beta 2 agonists?

Answer 37

Hydrogen bond

Question 38

What are the differences between beta 2 agonists and beta1 antagonists?

Answer 38

1) perpendicular ring 2) Alcohol group in S enantiomer 3) Short hydrophobic interactions

Question 39

What increases the activity of beta 2 agonists?

Answer 39

long hydrophobic chain separated by an ether

Question 40

Summarise the development of beta blockers

Answer 40

1) Alpha vs Beta selectivity - hydrophobic chain on amine 2) Agonist vs antagonist - linking group 3) Beta 1 vs beta 2 - hydrogen bonding group in para position