Receptor Theory 2 – Jenni Harvey PDF

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Part of the Receptor Theory series of lectures by Dr Harvey....

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Receptor Theory 2 – Jenni Harvey

 But Stephenson found drugs (eg. n-butyl trimethylammonium) acting as muscarinic R agonists in guinea pig ileum, where the ratio of agonist concentrations for 80% compared with 20% responses was much lower than 16 (i.e. concentration-response curves were much steeper than predicted by the occupancy equation).  Led to his modification of occupancy theory to incorporate influence of “spare receptors” upon agonist action Stephenson hypothesised that an agonist produces a response by applying a STIMULUS (S) to a tissue Size of the STIMULUS was thought to depend on two factors: (1) Agonist FRACTIONAL OCCUPANCY within the receptor population (2) Agonist EFFICACY (e) -the ability of the drug to produce an element of response when bound to each receptor. “bounce per ounce of agonist-bound receptor”.

 Efficacy was introduced by Stephenson (1956) to describe the way in which agonists vary in the response they produce even when they occupy the same number of receptors.  High-efficacy agonists produce maximal responses while occupying a relatively low proportion of receptors;  Lower efficacy agonists cannot activate receptors to the same degree and may not produce the same maximal response even when they occupy the entire receptor population, thereby behaving as partial agonists.

Stimulus and Efficacy MATHEMATICAL TREATMENT

S = e x = e x

fractional occupancy [D] [D] + Kd Divide top and bottom of

ratio by Kd, to rewrite equation as:

S =

e x

([D]/Kd) ([D]/Kd) +

1 When a very high proportion of spare receptors are present, agonist concentrations much lower than Kd would be required to produce responses up to the max response; in this case where [D]...