Met-enkephalin circulates in human plasma.

The physiological roles of Met-enkephalin and Leu-enkephalin are still unknown. They may act as neurotransmitters in the central and peripheral nervous systems. Met-enkephalin has been detected in several species in a variety of tissues including brain, spinal cord and gut using bioassays, opiate receptor assays and radioimmunoassays (RIA). It has also been detected in human gut immunocytochemically and in human brain and cerebrospinal fluid by opiate receptor assay and RIA. However, all reported assays show some degree of cross-reaction with Leu-enkephalin and unequivocal differentiation between the two enkephalins and the larger endorphins has not always been possible. Thus the existence of Met-enkephalin in human tissues and fluids remains in doubt. Using a highly specific RIA, we have now obtained evidence that Met-enkephalin-like material circulates in the plasma of normal subjects and may be secreted by the adrenal gland. Chromatographically the material exists in plasma mainly as the intact pentapeptide and not as the biologically inactive degradation product Gly-Gly-Phe-Met as would be expected from metabolic studies.