2. Receptors II Flashcards
Describe Negative co-operativity of a ligand binding drug.
Binding of a drug reduces affinity for binding of another ligand.
Describe positive co-operativity of a ligand binding drug.
Binding of a drug increases affinity for binding of another ligand.
Give the equation for Fractional Occupancy (r) using KD.
r = [D}]
[D]+KD
When r = 1/2 [D]= KD
Describe the shape of a plot of Fractional Occupancy against [D]
Regular hyperbola where r will level out at a concentration of full saturation of receptors.
Describe the shape of a plot of fractional occupancy against log[D].
Sigmoid curve. Between 20-80% fractionl occupancy will increase linearly.
Describe Occupation theory.
Response [E] ∝ number of receptors occupied
Describe pD2
the negative log of the agonist or [D] that gives a half-maximal response E/Emax
pD2 is a very useful pharmacological parameter as it quantifies the affinity of an agonist for its receptor, but this is not always correct as for many receptors occupational theory overestimates the kD so we may think the drug will bind tighter than it does.
Give the Assumptions of the Occupancy theory.
There are specific receptors for specific agonists
All agonists for a given receptor can produce the same maximum response.
The drug-receptor interaction is rapidly reversible
All receptors are equally accessible to the drug
The receptors do not interact with each other
The maximum response occurs when all the receptors are occupied
Describe a Partial Agonist.
an agonist drug that acts on a receptor and only produces a weak response.
Describe the problem with Occupancy theory for the assumption:
All agonists for a given receptor can produce the same maximum response.
-Some agonists drugs act on receptors and only produce a weak response, partial agonists
-Some agonist drugs are partial agonists so you need to introduce the concept that drugs may differ in their ability to induce a conformational change in the receptor once they have bound eliciting an effect.
Describe the problem with Occupancy theory for the assumption:
The maximal response occurs when all the receptors are occupied:
-Drugs that are very efficacious only a small percentage of total receptors are required to be bound to produce a maximal response leaving spare receptors.
-So if a irreversible antagonist is added and takes out 30% of receptors for a high efficacy drug and a higher concentration it may still be able to produce a max effect.
