Receptor Ligands

What is the two state receptor model?

• R → inactive receptor

• R* → active receptor

What is the basal state?

• receptors in cell with NO ligands present

How do active receptors differ from inactive receptors?

• active binds the G protein

• inactive does not

What is the distribution of active and inactive receptors with no ligand present?

• ~5% are active

• inactive receptors are more energetically favorable

What happens if a ligand that is an agonist binds to the receptor?

• agonist has preferential affinity for the active state of receptor

• more L = more [R*L]

What happens if a ligand that is an antagonist binds to the receptor?

• preferential affinity for INACTIVE receptors

• called an inverse agonist

What happens if a ligand that is a partial agonist binds to the receptor?

• binds BOTH active + inactive receptors

  • more active bound

  • only some inactive bound

What determines the affinity of a ligand for a target?

• # of bonds

• strength of bonds

What is the equilibrium dissociation constant (k_D)?

• measure of affinity

• lower the # → higher affinity

1 um =

1000 nM

1 mM =

1000 uM

How do agonists, partial agonists, neutral antagonists and inverse agonists differ in their affinity for various receptor conformations?

• partial agonists → higher affinity for active

T/F: In a partial agonist, the ligand will NEVER get 100% of active receptors?

TRUE

The dissociation constant (K_D) is a measure of a drug’s:

a. selectivity

b. efficacy

c. activity

d. none of these answer choices are correct

D

• measure of AFFINITY

_____________ displays both agonistic and antagonistic effects. In the presence of a ___________, a partial agonist will act as a(n) _____________.

a. Partial agonist, inverse agonist, full agonist

b. Inverse agonist, full agonist, antagonist

c. Full agonist, neutral antagonist, partial agonist

d. Partial agonist, full agonist, antagonist

D

A drug has a Kd = 3nM for its active form and a Kd =600 nM for the inactive form. Does this drug have greater affinity for the inactive or active receptor? And what type of agonist is it?

a. Inactive; partial agonist

b. Inactive; inverse agonist

c. Active; partial agonist

d. Active; inverse agonist

C

• lower Kd = higher affinity

• partial Ag bc it has affinity for both forms, but still more active than inactive

The ED₅₀ is a measure of the _____ of a drug. It’s the dose of the drug that produces a desired response in ___ of the population.

potency, 50%

Drug A and B both bind to the same receptor. Drug A has a Kd of 0.3 nM and Drug B has a Kd of 0.2 mM. Which of the following is true?

a. Drug B has a higher affinity than Drug A

b. Drug A has higher selectivity than Drug B

c. Drug A has lower affinity than Drug B

d. Drug A has higher affinity than Drug B

e. More information is needed

D

• 0.2 mM → 200,000 nM

• ****lower Kd = higher affinity

  • 0.3 nM > 200,000 nM