SIMILARITIES IN CELLULAR EXPRESSION AND FUNCTIONS OF MELANIN-CONCENTRATING HORMONE AND ATRIAL-NATRIURETIC-FACTOR IN THE RAT DIGESTIVE-TRACT

Melanin-concentrating hormone (MCH) is a cyclic peptide isolated first from salmon brain, then from rat and human hypothalamus. We have rece ntly found expression of MCH messenger RNA and encoded peptides, e.g. MCH and neuropeptide-glutamic acid-isoleucine, within the rat gastroin testinal (GI) tract, but their cellular origin was unclear. Furthermor e, similarities in the localization of rat atrial natriuretic factor ( ANF) and rat MCH immunoreactivities within intestine suggested functio nal convergence. In the present study we determined first the presence and distribution of MCH messenger RNA and encoded peptides in the GI tract by combining in situ hybridization and immunohistochemical analy sis. Our data revealed numerous MCH-containing cells located in the la mina propria and submucosa at both duodenal and colonic levels. Second , the localization of MCH- and arginine vasopressin- or ANF-containing cells appears similar at the duodenal and colonic levels, respectivel y. Colocalization of MCH/neuropeptide-glutamic acid-isoleucine immunor eactivity (-IR) and catecholamine indicated that MCH-expressing cells are probably antigen-presenting cells forming part of the enterochroma ffin cell system. Third, we performed reverse phase HPLC coupled to RI A to characterize MCH-like materials in different portions of the rat gut. Crude acidic extracts of rat intestine contained about 2-3 pmol/g tissue of MCH-IR, close to the values found in brain extracts. Revers e phase HPLC of MCH-IR in the GI tract revealed that only 10-30% of th e immunoreactivity corresponded to mature MCH, whereas the rat brain c ontained 94% mature peptide. Finally, we compared the effect of MCH an d ANF on water and electrolyte secretions at different levels of the G I tract by using the in situ ligated loop technique. Similar effects w ere noted for ANF and MCH; both stimulated water, Na, and K fluxes at the proximal colon level and increased Na and K fluxes in the duodenum . However, only ANF increased water and Cl fluxes in the duodenum and decreased bicarbonate secretion in the ileum, whereas MCH increased bi carbonate absorption in the jejunum. The dose required was 10 nmol/100 g . h for MCH, i.e. 10 times more than for the ANF. These studies str ongly suggest that MCH produced by antigen-presenting cells of the lam ina propria may have an important role, similar to that of ANF at the colonic level, in the physiology of the GI tract.