Agonists and antagonists

Question 1

Ways of regulating cell function

Answer 1

• altered membrane potential
• altered enzyme activity
• altered gene expression

Question 2

Effects of drugs

Answer 2

• agonism; produces effects
• antagonism; blocks effects
• densensitisation; reduces effects

Question 3

The patch clamp technique

Answer 3

A method of measuring the activity of a single ionotropic receptor. Uses an electrode within a micropipette to measure the response as a quantifiable current.

Question 4

Inverse agonists

Answer 4

Have negative efficacy, as they reduce spontaneous opening of ion channels.

Question 5

Super-agonists

Answer 5

Highly efficacious agonists that can produce a maximal response from the cell without binding to all of the available receptors. Emax is above 100%.

Question 6

Spare receptors

Answer 6

Receptors that are free/unbound after a maximal response has been produced by a super-agonist.

Question 7

Partial agonists

Answer 7

Low efficacy agonists that cannot produce the cell’s maximal response, even when they have bound to all of the available receptors.

Question 8

Types of antagonist

Answer 8

• competitive antagonist
• irreversible antagonist
• allosteric/ non-competitive antagonist
• channel blockers
• physiological antagonist

Question 9

Competitive antagonists

Answer 9

Bind reversibly at the same site as the agonist, producing a parallel shift to the right of agonist/dose response curves. The initial response to the agonist is reduced, but with increasing agonist concentration the maximal response can eventually be reached.

Question 10

Irreversible antagonists

Answer 10

Bind irreversibly by forming a covalent bond or binding very tightly at the same site as the agonist, decreasing the maximal response. Newly classified as protein degradation inducers.

Question 11

Allosteric antagonists

Answer 11

Bind reversibly at a distinct site from the agonist, decreasing agonist affinity and reducing the likelihood of agonist binding.

Question 12

Channel blockers

Answer 12

Bind inside the channel and prevent the passage of ions. Binding tends to be enhanced by receptor activation.

Question 13

Physiological antagonists

Answer 13

Antagonise the physiological effect of some agonists, but via a different mechanism.

Question 14

Desensitisation

Answer 14

The prolonged or repeated exposure to an agonist reduces the response to that drug. Mechanisms include up-regulation of the receptor, or up-regulation of the degrading enzyme for the respective drug.

Question 15

Receptor classification

Answer 15

Receptors are named according to the transmitter or hormone with which they interact. Most hormones interact with more than one type of receptor, and differences in protein structure underlie differences between subtypes.

Question 16

Receptor super-families

Answer 16

• integral ion channels eg. nicotinic receptor, glycine receptor
• integral tyrosine kinases eg. insulin receptor
• steroid receptors/nuclear receptors eg. estrogen receptor, androgen receptor
• G-protein coupled receptors
• cytokine receptors

Question 17

Allosteric effects on GABAa receptor

Answer 17

GABAa receptors are ligand-gated chloride channels found in the brain. Benzodiazepine agonists bind and increase the affinity of the GABA binding site, thereby increasing channel opening leading to a Cl- influx.

Question 18

Steroid/nuclear receptors

Answer 18

• act in the nucleus, but are most often located in the cytoplasm
• contain a ligand binding domain (LBD), which functions like a folding sensor; folded with steroid, unfolded without
• contain a DNA binding domain (DBD), which mediates binding to the genome
• contain a response element (RE)

Question 19

G-protein coupled receptors

Answer 19

• comprised of 7 transmembrane helices associated with proteins
• homo or hetero dimers
• many GPCRs (~4% of genome)
• several G subunits (Gs, Gi, Gq)

Question 20

Cytokine receptors

Answer 20

Similar to tyrosine kinase receptors, but only have a long peptide intracellularly.