Proenkephalin A-derived peptides in the human gut.

The intramural distribution of the proenkephalin A-derived peptides Leu5-enkephalin, Met5-enkephalin, Met5-enkephalin-Arg6-Phe7, and Met5-enkephalin-Arg6-Gly7-Leu8 was studied throughout the human gastrointestinal tract. A parallel distribution was found of Leu5/Met5-enkephalin, measured with a Leu5-enkephalin antiserum that cross-reacts about 30% with Met5-enkephalin, and of Met5-enkephalin-Arg6-Phe7-immunoreactivity and Met5-enkephalin-Arg6-Gly7-Leu8-immunoreactivity. In each case, high tissue concentrations were present in the submucosa and muscularis corresponding to the pyloric sphincter. Taking all different regions together, a high correlation was revealed between tissue levels of Leu5/Met5-enkephalinlike peptides and Met5-enkephalin-Arg6-Gly7-Leu8-like peptides (r = 0.89), as well as between Met5-enkephalin-Arg6-Gly7-Leu8-like peptides and Met5-enkephalin-Arg6-Phe7-like peptides (r = 0.75). Met5-enkephalin-Arg6-Phe7 immunoreactivity was accounted for by a major peak (87% +/- 3% of total immunoreactivity) coeluting with the standard peptide in Sephadex G-50 chromatography and largely composed of the authentic heptapeptide, as shown by reverse-phase high-performance liquid chromatography. Leu5/Met5-enkephalin immunoreactivity was separated by high-performance liquid chromatography into peaks composed of Leu5-enkephalin and Met5-enkephalin. Allowing for Met5-enkephalin immunoreactivity in the assay used, the apparent Leu5/Met5-enkephalin molecular ratio was approximately 1:4. The high concentration of all peptides studied at the pyloric junction suggests a rich enkephalin-containing innervation at this level, in keeping with the proposed involvement of an enkephalinergic mechanism in the control of pyloric function.