The receptor concept: prejudice, prediction, and paradox.
Major  progress has been achieved in understanding the chemical nature of receptors for certain hormones and neurotransmitters. Some of these units have been obtained as homogenous proteins; concept and technology are adequate to permit the detailed chemical and structural analysis of these macromolecular units. The critical problem which now arises is to define how a receptor once "occupied" and "activated" serves to initiate action. Elucidation of details of receptor structure, in of itself, will not solve the "coupling problem" in hormone action. New concepts, as well as new technics, will probably be necessary. In this discussion I have raised the possibility that metals coordinated to hormone receptor complexes may be the "trigger" element involved in initiating action, serving to alter the state of functional units in binary fashion. In effect, the metal determines whether the "state" of the system is active or inactive. As stated previously in connection with the action of steroid hormone receptor complexes, the specific suggestions made relating metals to the hormone coulping process have been advanced primarily to illustrate the conceptual gap which exists with respect to "coupling." The present suggestions may prove to be correct or untenable, in whole or in part. If it turns out that metals play a central role in the coupling process of hormone action, perhaps via completely different mechanisms than those suggested here, one of the central ideas of receptor action developed by the pioneers who created the receptor concept will have been resurrected in principle, if not in detail. In science, as in life generally, conceptual progress once achieved sometimes turns out to be the rediscovery of the past.
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D007257:Information Theory; D007476:Ionophores; D007679:Kidney Medulla / Q000201:enzymology; D007700:Kinetics; D008670:Metals / Q000502:physiology; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000302:isolation & purification / Q000502:physiology*; D012586:Science; D014667:Vasopressins / Q000378:metabolism
D007476:Ionophores; D008670:Metals; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D014667:Vasopressins; D000262:Adenylyl Cyclases