Identification and characterization of a novel gastric peptide hormone: The motilin-related peptide

Background & Aims: This study looked for new proteins with expression restr icted to the gastric epithelium that may provide insight to the differentia tion and function of the gastric unit, Methods: A novel complementary DNA w as isolated and sequenced, and its expression was examined in mouse tissues at both messenger RNA and protein levels, Subcellular localization was stu died using immunoelectron microscopy. The posttraductional processing of th e protein was analyzed in vitro by protein microsequencing and in vivo by W estern blotting, Results: We identified a novel protein that is mainly expr essed by the secretory granules of the stomach enteroendocrine cells, This protein has sequence similarity with prepromotilin, the precursor of the mo tilin hormone and the motilin-associated peptide. As for the prepromotilin, a posttraductional maturation leads to a secreted peptide that is further cleaved at a dibasic site and gives rise to the motilin-related peptide (MT LRP) and MTLRP-associated peptide. Conclusions: We have identified and char acterized a novel gene encoding the preproMTLRP protein. MTLRP presents sim ilarity to motilin and is specifically expressed by enteroendocrine cells o f the stomach and therefore represents a novel hormone.