Analysis of Neuroreceptor Binding In Vivo

Abstract

A number of biologically important drugs and chemicals that act in the brain do so specifically, that is, by association with membrane proteins designed to receive endogenous neurotransmitters and neuromodulators, although the endogenous ligands may not always be known. The existence of chemical receptorswas suspected before the turn of the century in the form of Langley’s concept of a “receptive” substance (Langley 1878) and Ehrlich’s “side-chain” theory (Ehrlich 1909), but modeling did not begin until the discovery of the binding of oxygen to specialized proteins, which made direct observation of receptor–ligand interaction possible. When the binding of oxygen to myoglobin was first observed to be a function of the oxygen tension in the solution (Bohr 1885), the relationship between the quantities of bound and free oxygen corresponded exactly to the relationship between the invertase reaction velocity and substrate concentration later derived by Michaelis and Menten (1913). Bohr (1904) published an equation for the interaction between hemoglobin and oxygen that antedated the equation suggested by Hill (1910) for receptor sites that interact cooperatively.

Adapted from Gjedde and Wong (1990) Compartmental analysis, in Quantitative Imaging: Neuroreceptors and Neurotransmitters, edited by J. James Frost and Henry N. Wagner, Jr., New York: Raven Press, Ltd. with permission from Raven Press, Ltd.