Opioids and their complicated receptor complexes.
No field more eagerly awaits a molecular clarification for G-protein coupled receptor (GPCR) dimerization than the opioid receptor field. Extensive evidence of pharmacological and functional interactions between opioid receptor types has primed this field for such a resolution. In retrospect, much of the data collected on synergy between different opioid receptor types may represent the functional correlate for the newly found opioid receptor dimerization. While previous reports of functional synergy have been, for the most part, consistent in demonstrating cross-regulation between two receptor types, the lack of highly receptor-selective ligands allowed skeptics to remain doubtful over the interpretations of these results. Today, two important developments in the opioid receptor field help reinvigorate the hypothesis of functional, cross-modulating opioid receptor complexes: (1) The existence of highly selective ligands which eliminate any possibility of cross-reactivity between receptor types, and (2) the discovery that opioid receptors 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 understand the mechanisms and implications of dimerization. Initial results of these studies have demonstrated that the dimerization of opioid receptors may help consolidate several pharmacological findings that have remained unanswered. In this review we present biochemical, pharmacological and functional evidence for opioid receptor complexes and add evidence from our recent studies on opioid receptor dimerization. We believe a thorough understanding of receptor dimerization is crucial in clarifying the mechanism of action of opioids and other drugs and may serve a more practical purpose in aiding the development of novel therapeutic drugs.
Jordan
B A
BA
Department of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Cvejic
S
S
Devi
L A
LA
D000818:Animals; D006801:Humans; D009294:Narcotics / Q000378:metabolism / Q000494:pharmacology*; D009420:Nervous System / Q000378:metabolism; D011957:Receptors, Opioid / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*
D009294:Narcotics; D011957:Receptors, Opioid