12: Receptor Theories Flashcards
what are the four major types of receptors?
- ion channel-receptors
- G-protein coupled receptors (GPCRs)
- receptor tyrosine kinases
- nuclear receptors
what is signal transduction?
the process of transmitting a signal from extracellular ligands to regulate intracellular processes
can a ligand bind to multiple receptors?
yes. a given ligand can bind to different receptors or different cells and mediate different intracellular changes.
what is considered the first messenger?
the extracellular ligand that binds a receptor on the outside
what is considered the second messenger?
the intracellular ion or molecule that changes as a result of the ligand binding and triggers a response
list and describe the three actions of receptors
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
how is the magnitude of the body’s response, drug-receptor interaction, and administered dose related to each other?
the more drug there is –> more drug-receptor interactions –> greater biological response
explain occupancy theory
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
explain rate theory
the frequency of receptor interactions
- how long does the drug stay bound to the receptor?
occupancy theory: how do you calculate Kd?
Kd = [L][R]/[LR]
the lower the Kd, the stronger the interaction
what is fractional occupancy and how do you calculate it?
fraction of receptors that have a drug bound to them
f = [LR]/([R] + [LR])
what is EC50? what does it tell you?
the concentration of ligand that gives 50% of maximal response
- tells you how well drugs work
- stronger drugs have lower EC50
what is the difference between an agonist and antagonist?
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
explain full versus partial agonists.
full agonist - large stimulus to cellular signaling machinery –> large effect
partial agonist - small stimulus to cellular signaling machinery –> small effect
what is the efficacy of a full agonist? partial agonist?
a - efficacy
full agonist = 1
partial agonist = 0 < a < 1
explain what would happen if you add partial agonist where there is maximal binding of full agonist already.
It will impede on the efficacy of the full agonist and decrease full agonist binding.
what is an indirect agonist?
a ligand that binds to a different (allosteric) site, but stimulates the same response
- doesn’t interfere with endogenous ligand binding
what is an inverse agonist?
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
what is the difference between agonist+no antagonist versus agonist+antagonist?
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
compare competitive antagonism and irreversible antagonism and their effect on efficacy
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
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?
nothing will happen bc agonists will counteract eachother
what is the difference between affinity and efficacy?
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
how are potency and efficacy different?
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
