Enkephalin/endorphin-related peptides in antropyloric gastrin cells.

Abstract

Immunocytochemistry reveals the presence of met-enkephalin-like immunoreactivity in antropyloric gastrin cells of man, pig, guinea pig and rat stomachs. Leu-enkephalin-like immunoreactivity cannot be detected in these cells. Antibody characterizations show that antibodies requiring the free COOH-terminal end of met-enkephalin fail to react with gastrin cells; antibodies capable of recognizing COOH-terminally elongated met-enkaphalin congeners, like .alpha.-endorphin, react. These results provide an explanation to previous data suggesting or denying the existence of met-enkephalin-like immunoreactivity in gastrin cells. The staining obtained cannot be explained by cross-reactivity to gastrin-17 or to ACTH-related peptides, but appears to result from a COOH-terminally elongated met-enkephalin congener. Such a molecule could represent either a biosynthetic precursor to met-enkephalin or a .beta.-endorphin-related peptide. Immunocytochemical double staining experiments reveal that the enkephalin-immunoreactive peptide(s) occur in only a subpopulation of the gastric cell cytoplasmic granules. This may indicate differences in the proteolytic processing of precursors or suggest that sequestration and intracellular transport of the enkephalin-like peptides differ from that of gastrin. Similar enkephalin/endorphin immunoreactivity is detected in human, but not in porcine or cavian, cholecystokinin cells. Biosynthesis experiments, utilizing isolated rat antropyloric mucosae in organ culture support the immunocytochemical observations by demonstrating incorporation of 35S-methionine, but not 3H-proline, into a specifically immunoprecipitable peptide, which in several chromatographical systems is indistinguishable from met-enkephalin. Apparently antropyloric gastrin cells actively form enkephalin/endorphin-related peptides. The possible biosynthetic relationship of these peptides to the ACTH-like peptides previously detected in gastrin cells, remains to be investigated.