Antagonism of receptor-activated biological effects mediated by second messenger pathways

It is generally held that many biologically active compounds produce their effects through a sequence of events that are initiated when the substances combine with selective receptors located on the cell surface membrane. Activation of these receptors produces a stimulus that is somehow transmitted intracellularly. The transduction between the stimulus and the response is now known to be mediated, in many systems, by an intracellular intermediary or second messenger. A model describing the relation of agonist concentration, receptor occupation, and biological response in such a system is herein extended to include antagonist binding at two target sites the cell-surface receptor and the receptor for the second messenger. It is demonstrated that the shift of an agonist's dose-response curve is characteristic of the site of antagonism and that analysis of this shift can reveal the existence of a second messenger pathway or, if this is known, the site of action of the antagonist.