Receptors and membrane signalling

Question 1

Competitive reversible antagonists

Answer 1

Produces a parallel shift to the right of the agonist dose/response curves (to the agonist)

Competing with the agonist for the same binding site
e.g atropine at muscarinic receptors, propanolol at b-adrenoreceptors

antagonist will win if it is in a higher concentration

Both agonist and antagonist bind reversibly; compete for same binding site
Presence of the antagonist decreases the probability of agonist binding.
‘Naloxone’ antagonist

Question 2

Concentration ratio (dose ratio)

Answer 2

the ratio of the concentration of agonist that produces a specified response (e.g EC50), in the presence of an antagonist, to the agonist concentration that produces the same response in the absence of the antagonist

Question 3

Effect of a full agonist in the presence of a partial agonist

Answer 3

Increasing the concentration of the partial agonist can eventually outcompete full agonist
Partial agonist ‘looking like’ its an antagonist as it is preventing full agonist reaching receptor.

Question 4

Irreversible antagonists

Answer 4

Competes with agonist for the same binding site
antagonist binds irreversibly
Presence of antagonist decreases number of available receptors
Decreases maximal response
Still possible to get maximal response despite the same presence of antagonist –> SPARE RECEPTORS

Question 5

Non-competitive antagonist

Answer 5

Binds at a DIFFERENT BINDING SITE
Prevents effect of agonist, without preventing its binding
Effect of NCA is insurmountable i.e an increase in agonist has NO effect (cannot be overcome)
Does not change the EC50 for the agonist

Question 6

Allosteric antagonists

Answer 6

Bind reversibly at other site other than AS
Decrease agonist affinity; reduces likelihood of agonist binding
Betacarbolines at GABAa receptor

Question 7

Channel blockers

Answer 7

Binds INSIDE channel and prevents the passage of ions
Binding of channel blockers tends to be enhanced by receptor activation (use dependence)
e.g phencyclidine at NDMA receptors

Question 8

Physiological antagonists

Answer 8

Ach and adrenaline on the heart

Produce opposite effects on a tissue
Providing a non-selective suppression of the response: not working via the same receptor agonist working from
Two drugs providing opposite effects

Question 9

Desensitization

Answer 9

Prolonged or repeated exposure to an agonist reduces the response to that drug
e.g tolerance to heroin; complementory increased adenylyl cyclase activity in the brain

Nicotinic receptors driven into inactive state