Receptor discrimination and control of agonist-antagonist
binding.
Tallarida, Ronald J.
Temple University School of Medicine, Philadelphia, PA 19140
APStracts 2:0095E, 1995.
The law of mass action is the common model for the interaction of
agonist and antagonist compounds with cellular receptors. Parameters
of the interaction, obtained from both functional and radioligand
binding studies, allow discrimination and sub-typing of receptors and
aid in understanding specific mechanisms . This article reviews the
theory and associated mathematical models and graphical
transformations of data that underlie the determination of receptor
parameters. The main theory assumes that agonist and antagonist
compounds bind to cells that have a fixed number of receptors and
provides the framework for obtaining drug-receptor parameters from
data and their graphical transformations. Conditions that produce a
change in receptor number, a newer concept in pharmacology, can have
an important effect on the parameter values derived in the usual way.
This review concludes with a discussion of the quantitative study of
receptor-mediated feedback control of endogenous ligands, a very new
topic with potentially important implications for understanding
antagonist effectiveness, loss of control and chaos in regulated
mass-action binding.
Received 6 October 1994; accepted in final form 20 March 1995.
APS Manuscript Number E415-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.