µ-Opioid Receptor

Abstract

It was reported in the 1960s that opioids show various actions through specific opioid receptors in in vitro studies (Kosterlitz and Watt, 1968). In 1971 and 1973, opiate receptors were reported by several independent investigators, in a ligand binding study in brain membranes (Goldstein et al., 1971; Pert and Snyder, 1973; Simon et a1.,1973; Terenius, 1973). The study of opioid receptors was accelerated by the discovery of endogenous opioids, such as enkephalins (Hughes et al., 1975), β-endorphin, dynorphin, and their related peptides (Goldstein, 1984; Yamashiro and Li, 1984). Biochemical, pharmacological, and behavioral studies provided the evidence that various actions of opiates and opioid peptides in the brain and peripheral tissues are mediated by interactions with different subtypes of opioid receptors, such as µ-, δ-, and κ-opioid receptors (Martin et al., 1976; Lord et al., 1977). Furthermore, the discovery of selective ligands for each subtype of opioid receptor (Paterson et al., 1984) made it easy to study the receptor subtype-specific responses in vivo and in vitro. For instance, in in vivo studies, the µ-opioid receptor is thought to be closely relevant to the production of analgesia in the brain (Satoh et al., 1983; Porreca et al., 1984). On the other hand, there are accumulating findings in vitro that µ- and δ- receptors are functionally coupled to the stimulation of potassium ion channel activity (North et al., 1987), whereas κ-receptor indicates an inhi-bition of calcium ion channel activity (Gross and Macdonald, 1987). In addition, µ-and δ-receptors are functionally coupled to the inhibition of adenylate cyclase in membranes of the brain and NG108-15 cells (Collier and Roy, 1974; Klee and Nirenberg, 1976).