Opioids: molecular basis of action

Regulation of the opioid neurotransmitter system is governed by three G protein–coupled receptors (GPCRs), (μOR, δOR, and κOR respectively), which bind and mediate the effects of the endogenous opioid peptides. Analgesic opiates such as morphine exert their effects by modulating this endogenous system and are indispensable therapeutic agents in the treatment of pain. Opioid research of the past decade has focused on understanding the molecular mechanisms that underlie the well-characterized physiologic effects of this neuroendocrine system. This review highlights year 2000 advances in opioid research that emphasize the molecular basis of opioid action. Advances in the fields of opioid system homeostasis, opioids and diabetes mellitus, structure–activity relationships, morphine tolerance and dependence, receptor trafficking and signaling regulation, and receptor hetero-oligomerization are discussed in the context of their potential clinical applications and their contributions to our understanding of opioid system function.