Kinetic versus allosteric mechanisms to explain insurmountable antagonism and delayed ligand dissociation.
The present review addresses the theories which have been advanced to explain experimental observations dealing with insurmountable antagonism and accelerated radioligand dissociation in the presence of an excess unlabelled ligand. We came to the perception that, for each of these phenomena, the theories can be placed into two distinctive categories. The "kinetic" interpretations attribute these phenomena to, respectively, the ability of antagonists to form long-lasting complexes with their cognate receptor and the ability of dissociated ligands to bind again to the same or neighbouring receptors rather than to diffuse away from the cell surface. On the other hand, these observations can also be explained by negative allosteric interactions among topographically distinct ligand binding sites at the same receptor or di/multimeric receptor complex.
Vauquelin
Georges
G
Department of Molecular and Biochemical Pharmacology, Free University of Brussels (VUB), Building E.5.10, Pleinlaan 2, Brussel B-1050, Belgium. gvauquel@vub.ac.be
Szczuka
Anna
A
D000818:Animals; D004336:Drug Antagonism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology; D011955:Receptors, Drug / Q000737:chemistry / Q000187:drug effects*
D008024:Ligands; D011956:Receptors, Cell Surface; D011955:Receptors, Drug