LOW-SALT INTAKE DOWN-REGULATES THE GUANYLIN SIGNALING PATHWAY IN RAT DISTAL COLON

Background & Aims: Guanylin, an endogenous gastrointestinal peptide, c auses the translocation of NaCl from interstitial fluid to the intesti nal lumen. The aim of this study was to examine whether changes in die tary salt intake lead to compensatory changes in expression of the gua nylin signaling pathway. Methods: Rats received low-, normal-, or high -sodium diets for 1 week. Colonic guanylin expression was evaluated by Western and Northern blotting, rates of guanylin secretion by measuri ng biologically active guanylin released into the medium from colon ex plants, and expression of the guanylin receptor (C-type guanylate cycl ase) by Northern blotting and bioassay. Results: By every criterion, t he low-salt diet reduced expression of guanylin to 30%-40% of the leve l found in control animals. Guanylin receptor expression was also decr eased, although less dramatically and with a lower statistical signifi cance. For both guanylin and guanylin receptor, the high-salt diet had no significant effect on expression. Conclusions: The data support th e hypothesis that the guanylin pathway is down-regulated as an adaptiv e response to salt restriction.