Tryptophylglycine dipeptide in ACTH/MSH cells of the human hypophysis: its identification and studies on its antinociceptive effects in mice.

The ACTH/MSH cells of the pars distalis and pars intermedia of the mammalian hypophysis contain peptides with amino-terminal tryptophan which exhibit a strong fluorescence after treatment with modified formaldehyde vapour methods and with glyoxylic acid in the tissue sections from freeze-dried specimens. By homogenization of the hypophyses in ethanolic glyoxylic acid and subsequent heating the peptides can be converted to highly fluorescent beta-carboline derivatives; these can then be extracted with glacial acetic acid, separated by silica gel thin-layer chromatography and identified in UV light. Amino-terminal tryptophyl peptide from adult human hypophysis extracted and treated in this way gave the structure L-tryptophylglycine after acid hydrolysis. This structure was subsequently confirmed by producing a fluorescent derivative from authentic L-tryptophylglycine using the same reaction conditions as for the tissue homogenate. This derivative moved in the same way in thin-layer chromatography as fluorecent amino-terminal tryptophyl peptide extracted from human hypophysis. Thereafter a study was made of the antinociceptive effects of authentic L-tryptophylglycine administered subcutaneously in mice both alone and together with morphine. L-tryptophylglycine had no antinociceptive effects alone and neither did it change morphine antinociception. Also it had no apparent effects on the behaviour of mice. Thus, ACTH/MSH cells contain a dipeptide whose physiological function differs from the effects of ACTH, MSH and endorphins.