Distribution and pharmacology of the enkephalins

Abstract

It is now just over two years since the publication of the structures of two peptides found in the brain which possessed potent opiate agonist activity (Hughes et al., 1975; Simantov and Snyder, 1976). These peptides were named enkephalins and had structures H₂ N-Tyr-Gly-Gly-Phe-Met-OH ([Met⁵]-enkephalin) and H₂ N-Tyr-Gly-Gly-Phe-Leu-OH ([Leu⁵]-enkephalin). The structure of [Met⁵]-enkephalin is contained in its entirety within the sequence of the hormone β-lipotropin (β-LPH), a 91-amino acid peptide in which [Met⁵]-enkephalin constitutes residues 61–65 (Hughes et al., 1975). Moreover, peptides with sequences ranging from β-LPH_61–65 ([Met⁵]. enkephalin) to β-LPH_61–91 all seem to possess opiate agonist activity (Bradbury et al., 1976a; Cox et al., 1976; Lazarus et al., 1976). Several of these related peptides, β-LPH_61–91 (β-endorphin), β-LPH_61–76 (α-endorphin) and β-LPH_61–77 (γ-endorphin) have now been isolated from the brain, pituitary or gastrointestinal tract of several species (Bradbury et al., 1976b; Bloom et al., 1978). These observations have stimulated research in many areas of neurobiology and results have been obtained suggesting that the opiate peptides have fundamental roles in many neuronal and endocrine mechanisms.