PH1125 - Receptors Flashcards
what is a receptor?
- protein macromolecule which is a recognition site normally activated by neurotransmitters. hormones or drugs
what are channel receptors? (3)
- hole in membrane
- allows passage of ions through membrane
- activation of conductance
what are g protein receptors? (3)
- receptor couples with g protein
- generates second messenger
- activation of signal in cell
what are enzyme receptors? (3)
- activation of enzyme that sits in membrane
- phosphorylation of key components in cell
- activation of cell signalling
what is a ligand?
- substance that interacts with a biomolecule to serve a biological purpose
what are examples of intermolecular forces? (4)
- electrostatic forces
- H bonding
- van der waals
- hydrophobic interactions
what is the intrinsic efficacy?
- ability of an agonist to alter receptor conformation to elicit a response
what is the maximum response?
- full occupation o receptors
- dose increase gives no bigger response
what is the threshold dose?
- sufficient receptors occupied to elicit a response
what is an agonist?
- a molecule capable of binding to and activating a receptor
what is a competitive antagonist? (2)
- receptor antagonist that binds to a receptor but does not activate the receptor
- will compete with available agonist for receptor binding sites on the same receptor
what is affinity?
- measure of how avidly the agonist (drug) binds to the receptor
what way does the curve shift with higher affinity agonist and agonist and why? (2)
- agonist curve shifts left
- binds to the receptor better therefore lower concentration required to elicit the same response
what way does the curve shift with lower affinity agonist and agonist and why? (2)
- agonist curve shifts right
- doesn’t bind as well to the receptor therefore a higher concentration is needed to elicit the same response as a higher affinity agonist
what is efficacy?
- relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level
what way does the curve shift with an agonist and an agonist with competitive antagonists and why? (3)
- agonist curve shifts right
- competitive antagonist sits and blocks the receptors
- agonist concentration needs to be increased
what is a functional non-competitive antagonist?
- second messenger pathway blocked by antagonist
what is an allosteric antagonist?
- drug that modulates the response of an antagonist but makes the receptor less effective
what way does the curve shift with an agonist and an agonist with irreversible antagonists (high dose) and why? (3)
- agonist curve shifts right and maximum tissue response decreases
- an irreversible antagonist reduces the pool of receptors
- blocked receptors results in reduced effect
what is the relationship between a full agonist and partial agonist when they compete?
- the partial agonist acts like a competitive antagonist
what are spare receptors?
- present in a system when full agonist produces a maximum response when only a fraction of the total receptor population is occupied
what is ec50 in term of occupancy and response? (2)
- 50% occupancy
- 50% response
D + R ⇌ DR
Ka and Kd?
- d is the concentration
- r is the receptor
- dr is the drug-receptor compex
- Ka (association constant) is the forward reaction
- Kd (disassociation constant) is the backward reaction
what is Ka? (2)
- high affinity vs low affinity
- BIG number
what is Kd? (2)
- related to concentration
- SMALL number
what is the equation for Ka in terms of Kd?
- Ka = 1/Kd
what are the Ka and Kd values useful for?
- useful for estimating how much drug to use and estimating relative selectivity
what is the schild equation?
- log (rose ratio - 1) = log [antagonist] - log (Kd)
- y = mx + c
for a competitive antagonist what is the gradient on a schild plot?
-1
what can cause a schild plot to differ from 1? (4)
- non-competitive antagonism; antagonist interacts with the receptor at non-overlapping site)
- drug disposition mechanism / other non-equilibrium steady state present
- competitive antagonism of a heterogeneous receptor population subserving the same response
- multiple drug effects occur
