Receptor Theory

Question 1

What is a ligand?

Answer 1

A ligand is something that binds to a target to excerpt an effect.

Question 2

What is an agonist?

Answer 2

A ligand that binds and then activates a receptor. Therefore an agonist has both affinity and intrinsic efficacy for the receptor.

Question 3

What is an antagonist?

Answer 3

An agonist is a ligand that binds to a receptor and blocks the binding of another agonist to prevent the activation of the receptor. Therefore an antagonist has affinity for the receptor but no intrinsic affinity (it doesn’t activate the receptor)

Question 4

What is an orthosteric site?

Answer 4

Where a ligand binds. The “active site”

Question 5

What is an allosteric site?

Answer 5

A site at which a ligand can bind and effect receptor activity that isn’t the main binding site.

Question 6

Define affinity.

Answer 6

A measure of the strength of interaction between the ligand and receptor. A giant must have affinity for a receptor in order to bind to it.

Question 7

Define efficacy.

Answer 7

Efficacy combines the ligands intrinsic efficacy and the response of the cell/tissue. So efficacy involves both the activation of the receptor and the response this causes in the cell.

Question 8

What is potency?

Answer 8

Potency depends upon affinity, intrinsic efficacy and the cell specific components forming an action. The ligand must bind, activate the receptor and then a response must occur. It is measured using EC50.

Question 9

What is intrinsic activity?

Answer 9

This is the ability of a ligand to activate or “turn on” a receptor and give it the potential to create/mediate a response in the cell or tissue.

Question 10

What is partial antagonism?

Answer 10

When an agonist binds and has intrinsic efficacy for a recpeptor but it is reduced. So it may be needed in higher concentrations to cause the same effect or may not reach full effect ever. The are agonists when in the presence of no other/low levels of competing agonist. But act as agonists in high levels of other ligand.

Eg heroin addicts

Question 11

What does the spare receptor theory explain?

Answer 11

Why Bmax platoes even if not all receptors are bound to. It means that not all receptors need to be bound to to create the maximum response. This could be because there is another limiting factor, for example a muscle can only contract a certain amount, a gland can only secrete so much, or amplification using enzymes may be at its max.

Question 12

What is selectivity and what is its importance?

Answer 12

A ligand can select for a specific receptor and only have affinity/bind to this. Selectivity can either be through affinity (only binds to certain receptor) or efficacy (only activates certain receptor). It can be on a scale, or select for multiple receptors. It is important in drugs as it can cause side effects if other receptors are activated.

Question 13

What is specificity and what is its importance?

Answer 13

Same as selectivity

Question 14

What is Kd?

Answer 14

It’s used as an index of affinity. The lower the value the higher the affinity of the ligand for the receptor. It is the concentration of ligand needed to occupy 50% of the receptors.

Question 15

What is Bmax?

Answer 15

The maximum binding capacity of the cells receptors (the total number of receptors that the ligand could possibly bind to)

Question 16

How are Kd and Bmax related?

Answer 16

Kd is found at half of Bmax (50% of receptors occupied). However Bmax measures maximum number of receptors and conc when reached so it changes. Kd always remains the same as its always the same conc of ligand needed to fill 50% of receptors as the ligands affinity doesn’t change.

Question 17

What is EC50?

Answer 17

A measure of potency. It’s the concentration of ligand needed to give 50% of the maximum response (Emax).

Question 18

What is Emax?

Answer 18

the maximum effect/response caused by the ligand binding to the receptors.

Question 19

How are Emax and EC50 lined?

Answer 19

EC50 is found using half of the Emax. Emax is just used to find maximum effect but EC50 can refer to the ligands potency.

Question 20

What is IC50?

Answer 20

The concentration of agonist that gives 50% inhibition of the response. It gives an indication of antagonist affinity but can also be influenced by the conc of antagonist and strength of stimulus.

Question 21

Describe what happens in reversible competitive antagonism.

Answer 21

Rely on dynamic equilibrium of ligand and receptor. They cause a parrelell shift to the right in the agonist concentration-response curve.

Question 22

Describe what happens in irreversible competitive antagonism.

Answer 22

Occurs when the antagonist dissociates slowly or not at all. Over time (or by increasing agonist conc) more receptors get blocked by the antagonist, and this is reversible. Over time much more high concentrations of agonist are needed to promote any repsonse if at all. Eventually there will be no response at all regardless of agonist conc

Question 23

What happens in non-competitive antagonism?

Answer 23

Antagonist binds at allosteric site (not ligand site). They enhance or reduce the effect of the agonist that later binds. There is no competition as the binding site remains free for the agonist to bind to

Question 24

How can we measure ligand binding?

Answer 24

Often by binding radioactively labelled ligands (radioligands) we can measure the number of bound or free ligands and compare it to the number of receptors we know are on the cell. Usually we measure the bound radioligands.