12: Receptor Theories

Question 1

what are the four major types of receptors?

Answer 1

• ion channel-receptors
• G-protein coupled receptors (GPCRs)
• receptor tyrosine kinases
• nuclear receptors

Question 2

what is signal transduction?

Answer 2

the process of transmitting a signal from extracellular ligands to regulate intracellular processes

Question 3

can a ligand bind to multiple receptors?

Answer 3

yes. a given ligand can bind to different receptors or different cells and mediate different intracellular changes.

Question 4

what is considered the first messenger?

Answer 4

the extracellular ligand that binds a receptor on the outside

Question 5

what is considered the second messenger?

Answer 5

the intracellular ion or molecule that changes as a result of the ligand binding and triggers a response

Question 6

list and describe the three actions of receptors

Answer 6

transducer
- when the ligand binds to the receptor, the signal needs to be passed on, often via a new form

discriminator
- specificity of the receptor (selectively responds to some signals)

amplifier
- can increase the magnitude of a response

Question 7

how is the magnitude of the body’s response, drug-receptor interaction, and administered dose related to each other?

Answer 7

the more drug there is –> more drug-receptor interactions –> greater biological response

Question 8

explain occupancy theory

Answer 8

the number of receptor interactions is going to determine the degree of response
- what fraction of the receptors is occupied by the drug?
- graph will eventually form plateau because of saturation of receptors and excess ligand

Question 9

explain rate theory

Answer 9

the frequency of receptor interactions
- how long does the drug stay bound to the receptor?

Question 10

occupancy theory: how do you calculate Kd?

Answer 10

Kd = [L][R]/[LR]

the lower the Kd, the stronger the interaction

Question 11

what is fractional occupancy and how do you calculate it?

Answer 11

fraction of receptors that have a drug bound to them
f = [LR]/([R] + [LR])

Question 12

what is EC50? what does it tell you?

Answer 12

the concentration of ligand that gives 50% of maximal response
- tells you how well drugs work
- stronger drugs have lower EC50

Question 13

what is the difference between an agonist and antagonist?

Answer 13

agonists are ligands that bind a receptor to stimulate a response.

antagonists are lingands that bind a receptor to inhibits an agonist response
- inhibits endogenous ligand from binding to receptor

Question 14

explain full versus partial agonists.

Answer 14

full agonist - large stimulus to cellular signaling machinery –> large effect

partial agonist - small stimulus to cellular signaling machinery –> small effect

Question 15

what is the efficacy of a full agonist? partial agonist?

Answer 15

a - efficacy
full agonist = 1
partial agonist = 0 < a < 1

Question 16

explain what would happen if you add partial agonist where there is maximal binding of full agonist already.

Answer 16

It will impede on the efficacy of the full agonist and decrease full agonist binding.

Question 17

what is an indirect agonist?

Answer 17

a ligand that binds to a different (allosteric) site, but stimulates the same response
- doesn’t interfere with endogenous ligand binding

Question 18

what is an inverse agonist?

Answer 18

a ligand that stimulates an opposite response of agonist and may or may not be binding to the same receptor as the agonist
- shifts the equilibrium to the formation of the inactive conformer
- a < 0

Question 19

what is the difference between agonist+no antagonist versus agonist+antagonist?

Answer 19

agonist+no antagonist: maxiumum potency and max efficacy

agonist+antagonist: reduced potency and max efficacy
- inhibits rate of maximal response so you need an increased agonist concentration to get to the same max efficacy

Question 20

compare competitive antagonism and irreversible antagonism and their effect on efficacy

Answer 20

competitive antagonism will have same max efficacy but reduced potency

irreversible antagonism will have reduced efficacy and reduced potency
- reduced efficacy because antagonist binding is permanent and cannot be overcome by adding more agonists

Question 21

Sometimes two different receptors may affect the same second messenger pathway and cause opposite effects. What would happen if agonists bind to each receptor at the same time?

Answer 21

nothing will happen bc agonists will counteract eachother

Question 22

what is the difference between affinity and efficacy?

Answer 22

affinity - the ability of the ligand to bind to a receptor target (how strongly do they bind?)

efficacy - the relationship between how many receptors are bound and the strength of its response

Question 23

how are potency and efficacy different?

Answer 23

potency describes the concentration at which half-max efficacy occurs (more potent = less concentration)

efficacy describes the max strength of the effect regardless of drug concentraion