ABSTRACT
The discovery of two endogenous opiate-or morphinelike peptides, Leuenkephalin and Met-enkephalin, by Hughes and colleagues in 1975 [1] led to the explosive advances in our understanding of the functions of opioid receptors and the actions of opiates and opioids in the last two decades. These two enkephalins are pentapeptides with identical first four amino acids of H-Tyr-Gly-Gly-Phe-OH and either leucine (Leu) or methionine (Met) at the fifth position carboxy-terminus. These two peptides were also later found to be derived from three separate precursor proteins produced from three genes known as preproenkephalin (or preproenkephalin A), preproopiomelanocortin (or pre-POMC), and preprodynorphin (or preproenkephalin B) genes [see reviews 2,3]. These endogenous morphinelike peptides were collectively classified as endorphins.
