ABSTRACT
The existence of endogenous receptors for opioids in 1973 [1-3] ignited the vigorous search for endogenous substances that act at these receptor sites. Furthermore, the existence of these receptors generated great interest in the exploration of endogenous pain mechanisms and modulation by inhibitory systems, as well as into biological mechanisms of opiate dependence and withdrawal. Recognition of the strong likelihood of multiple subtypes of opioid receptors came from the work of Martin [4]. It was found that vastly different behavioral syndromes were elicited in spinalized dogs by morphine, ketocyclazocine, and SKF-10,047 leading to the nomenclature of mu, kappa, and sigma opiate receptors, respectively [4,5]. The observation of differential binding affinities for [Met5]enkephalin and h endorphin against [3H][Leu5] enkephalin and [3H]naloxone in guinea pig brain and differential agonistic activity profiles of [Leu5]enkephalin and [Met5]enkephalin in the isolated mouse vas deferens and guinea pig ileum strongly supported the existence of the y-opioid receptor [6-8]. Over time, the existence of additional opioid
receptor subtypes has been hypothesized to include the epsilon receptor [9] and possibly others. The actual characterization of these additional receptors has not been achieved, and with the advent of molecular cloning of the opioid receptors, only three subtypes are generally accepted; namely, the mu, kappa, and delta (y) subtypes [10]. The existence of subtypes of these opioid receptors, including the y-opioid receptor have also been suggested, based on a broad array of approaches including pharmacological and receptor binding studies. Although different subtypes have not been cloned, it is possible for example that posttranscriptional events may occur to produce these subtypes [10]. Here, the pharmacology and physiology of the y-opioid receptors is discussed.
