Opioids and their complicated receptor complexes

No field more eagerly awaits a molecular clarification for G-protein couple d receptor (GPCR) dimerization than the opioid receptor field. Extensive ev idence of pharmacological and functional interactions between opioid recept or types has primed this field for such a resolution. In retrospect, much o f the data collected on synergy between different opioid receptor types may represent the functional correlate for the newly found opioid receptor dim erization. While previous reports of functional synergy have been,for the m ost part, consistent in demonstrating cross-regulation between two receptor types, the lack of highly receptor-selective ligands allowed skeptics to r emain doubtful over the interpretations of these results. Today, two import ant developments in the opioid receptor field help reinvigorate the hypothe sis of functional, cross-modulating opioid receptor complexes: (1) The exis tence of highly selective ligands which eliminate any possibility of cross- reactivity between receptor types, and (2) the discovery that opioid recept ors and a number of other GPCRs exist as dimers in biochemical, functional and pharmacological assays. It is with these new tools that we seek to unde rstand the mechanisms and implications of dimerization. Initial results of these studies have demonstrated that the dimerization of opioid receptors m ay help consolidate several pharmacological findings that have remained una nswered. In this review we present biochemical, pharmacological and functio nal evidence for opioid receptor complexes and add evidence from our recent studies on opioid receptor dimerization. We believe a thorough understandi ng of receptor dimerization is crucial in clarifying the mechanism of actio n of opioids and other drugs and may serve a more practical purpose in aidi ng the development of novel therapeutic drugs. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.