ABSTRACT
The endogenous opioid system includes four distinct neuronal pathways that are widely distributed throughout the central nervous system (CNS). The endogenous opioid peptides are mainly derived from four precursorsproenkephalin, proopiomelanocortin, prodynorphin, and pronociceptin/ orphanin FQ-and exert their physiological actions by interacting with various classes of opioid receptor types-mu, delta, kappa, and Noc/ORL1present on both pre-and postsynaptic membranes of opioid and opioidtarget neurons. The most important opioid peptides seems to be the pentapeptides enkephalins [1], which interact with both mu and delta receptors, their affinities being significantly better for the latter. This has triggered intensive studies to elucidate the role of enkephalins in the brain and to develop putative novel effective treatments mainly in the field of analgesia and CNS disorders [2]. Moreover, the presence of peripheral enkephalin-controlled peripheral systems such as intestinal motility and fluid secretion, or heart rhythm, constitute interesting clinical targets. The most simple and efficient means to investigate the respective physiological roles of mu and
delta receptors is to analyze the responses generated by an enhancement in the levels of synaptic enkephalins and their prevention by selective antagonists of both kinds of binding sites. The specific delta responses observed by this approach based on the use of enkephalin-inactivating enzymes are summarized in this paper.
