Are receptors promiscuous? Intrinsic efficacy as a transduction phenomenon

The classical pharmacologic scales of agonist affinity and relative intrinsic efficacy, as utilized for drug and drug receptor classification, are examined in terms emerging concepts of receptor signal transduction. Specifically, evidence is considered that within the membrane of some cells, receptors may couple to more than one type of G-protein after agonist activation and that the relative dependence of response to different coupling proteins would make agonist efficacy a tissue dependent and not strictly a receptor dependent property. Since efficacy would depend upon the chemical nature of at least two receptor recognition domains (an extracellular domain for agonist recognition and a cytosolic domain for G-protein recognition), and agonist and antagonist affinity would depend upon only one, quantitative classification data utilizing these two scales would be divergent.