[Endorphins, opioid receptors and site of action of morphinomimetics]

Each class (mu, delta kappa and epsilon) of opioid receptors has a characteristic pattern of distribution in the nervous system, which may, however, exhibit species differences. The effects of opioid receptor stimulation depend on the class of receptor involved, the localization of these specific receptors and the animal species under investigation. Endogenous ligands of opioid receptors, which include more than twenty peptides, derive from three precursors:proopiomelanocortin (beta-endorphin), proenkephalin A (enkephalins) and prodynorphin (dynorphins, neo-endorphins). Generally, the endogenous ligands do not exhibit a marked selectivity toward a given receptor class. Most of the clinically used morphinomimetics, including morphine, bind preferentially to mu receptors. However, this interaction is not exclusive and these drugs are most often mixed ligands which also bind to the other classes of opioid receptors. Peripheral targets for morphinomimetics have been suspected for a long time, and recent data confirmed that opioids do act on receptors located on peripheral terminals of primary afferent fibers. The dorsal horn of the spinal cord is well known as a central site of action of morphinomimetics. At this level, opioids reduce the activity of spinal neurones that convey the nociceptive messages. The classes of opioid receptors (certainly mu [mu 2?] and a, perhaps kappa) involved in this effect, and their pre- or postsynaptic location are not firmly established to date. Further developments on these points can be expected from the use of new ligands which are highly selective of the various classes of opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)