Interpretation of agonist affinity estimations: the question of distributed receptor states - PubMed (original) (raw)

Comparative Study

. 1990 Jun 22;240(1299):503-18.

doi: 10.1098/rspb.1990.0051.

Affiliations

Comparative Study

Interpretation of agonist affinity estimations: the question of distributed receptor states

J W Black et al. Proc R Soc Lond B Biol Sci. 1990.

Abstract

In the receptor-transducer model of pharmacological agonism, rejection of the traditional assumption that receptor molecules are in vast excess of transducer molecules permits the receptors to become distributed among unbound, bound and complexed states. Under these conditions, agonist affinities are liable to be overestimated when the method of irreversible receptor antagonism is used. Graphical tests have been developed to detect distribution, and these were applied to experimental data from the interaction between 5-HT and phenoxybenzamine on aortic tissue. Significant receptor distribution was not detected by the method. However, in the model it was assumed that there was a linear relation between the concentration of ternary complex and pharmacological effect. If this relation was replaced with a saturable one the effect of receptor distribution would be masked. The implications for pharmacologists and medicinal chemists are discussed.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources