Proenkephalin-Derived Opioid Peptides

Proenkephalin-derived opioid peptides are processed from the preproenkephalin A gene and are distributed widely throughout the brain, but are also located in non-central nervous system (CNS) structures, such as the gastrointestinal system, cardiovsiscular system, and placenta. These opioid peptides bind to classical μ and δ opioid receptors, and function as neuromodulators. The basic science and clinical implications of the enkephalins are wide-ranging and have enormous potential. The native pentapeptides are not only produced by multiple genes, but have divergent functions and different sites of activity (i.e., receptors). Known to be conserved phylogenetically, enkephalins play a role in two very necessary processes of animal survival: growth and neurotransmission. As such, enkephalins have very broad-reaching implications in maintenance of mammalian homeostasis, as well as in various disease states. The opioid growth factor (OGF)-OGF receptor (OGFr) axis has been shown to be involved in the regulation of neoplasia, wound healing, normal homeostatic functions, embryonic development, and angiogenesis; other areas of activity have simply not yet been discovered. Mediation of enkephalin activity and harnessing the inhibitory action of enkephalins for therapeutic treatment and/or diagnostics has great clinical potential.