Mu opioid receptors: cellular action and tolerance development.

Opioids are some of the most effective pain-relieving drugs used in the clinical management of pain (Gilman et al. 1990). In addition to their analgesic effect, opioid peptides and alkaloids also affect a number of physiological functions including hormone secretion, neurotransmitter release, feeding, gastrointestinal motility, and respiratory activity (Pasternak 1988). Extensive physiological, behavioral, and pharma-cological studies have defined at least three major types of opioid receptors designated mu, kappa, and delta (Corbett et al. 1993; Goldstein 1987; Wood and Iyengar 1988). Although there is substantial overlap in their tissue distribution and pharmacological profiles, each opioid receptor type maintains a unique pattern of expression while displaying characteristic binding affinities for various subtype-selective ligands. The delta receptors that bind the enkephalin peptides are expressed most predominantly in the basal ganglia, striatum, and cerebral cortex (Mansour et al. 1988; Wood 1988). Although delta receptors have been implicated in spinal analgesia (Porreca et al. 1984; Yaksh 1981), recently it has been suggested that specific delta receptor subtypes may also be involved in supraspinal analgesia (Pasternak 1993). The kappa receptors are most highly expressed in cortex, striatum, and hypothalamus (Mansour et al. 1987), with various subtypes identified by autoradiography using subtype-selective ligands (Nock et al. 1988; Unterwald et al. 1991). With the development of more highly subtype-selective ligands, these receptors have been shown to mediate both spinal and supraspinal analgesia (Pasternak 1993).