Agonists Flashcards
What is a receptor?
A protein target with which a naturally occurring chemical mediator binds specifically to initiate a cellular response.
What route must a chemical mediator take if it is large and/ or hydrophilic?
They rely on cell surface receptors.
What route can a chemical mediator take if it is small and / or hydrophobic?
These can pass through the membrane and directly activate intracellular receptor proteins.
How would you describe the shape change of a receptor upon binding with a chemical mediator?
The shape change stabilises the active form of the receptor and enhances the interaction with signal transduction mechanism.
What are the five factors that affect the size of a response to a receptor agonist?
1) Concentration of drug (agonist)
2) Affinity of drug to receptor
3) Intrinsic efficacy (ability to activate)
4) Nature of receptor-response coupling
5) Total number of receptors present
When is a maximum response observed?
When all receptors present are occupied by the agonist.
How do you describe the binding of an agonist with a receptor?
Agonist receptor complex
The fraction of the total number of receptors available which are occupied depends on?
Agonist concentration
Strength of bonds formed
What is the rate of a reversible reaction proportional to?
The product of the concentration of the reactant
What is the equation for the forward rate of a reaction (K+1)?
[free receptor][agonist]
What is the equation for the backwards rate of a reaction (K-1)?
[agonist - receptor complex]
How do you describe the reaction rate at equilibrium?
Forward = backwards
K+1 [Ntot - Na] [Xa] = K-1 [Na]
Describe the equation
Ntot = total number of receptors present
Na = number of receptors occupied by agonist
Ntot-Na = number of unoccupied receptors
Xa = concentration of agonist within the vicinity of receptors
What is the fractional occupancy equation?
Na/Ntot = [Xa] / ([Xa] + Ka)
What is Ka?
Equilibrium constant for agonist A
How does the occupancy change as Ka changes?
The smaller Ka the higher the occupancy
The bigger Ka the lower the occupancy
What is important to remember about Ka at 50% occupancy?
Ka is numerically equal to the concentration of agonist when half of the total receptors present are occupied
Why is there lower binding with a higher Ka?
Higher Ka value means lower affinity (strength of binding) of agonist for receptor.
How is the actual response of a drug simulated?
Preforming a Bioassay
Outline the steps of a bioassay
Muscle strip (usually intestine) set up in an organ bath
Use a suitable physiological medium
Oxygenate the bath
Maintain physiologic temperature
When agonist is added record the rate of contraction seen using a computer programme
Define what an EC50 is
The effective concentration needed to produce 50% of the maximum response
What is the difference between Ka and EC50?
Ka is a theoretical measure of affinity of agonist receptor complexes as an isolated entity.
EC50 is practical and indirect, measures drug potency downstream of receptor. Relates agonist concentration to biological effect produced by
Describe receptor activation
(Intrinsic efficacy)
The ability of an agonist on binding to a receptor to activate a change in shape of the receptor
Shape change is needed to couple the receptor to the signal transduction mechanism
What do full agonists do?
Produce the maximum response of which the tissue is capable of during the activation of all that population of receptors
