GUANYLIN ACTIVATES RAT COLONIC PARTICULATE GUANYLATE-CYCLASE

The polypeptide guanylin is an endogenous activator of small intestina l guanylate cyclase. In rat, guanylin mRNA is found predominantly in i ntestinal tissues,with its highest abundance in the colon. To date, th e effect of guanylin on rat colonic particulate guanylate cyclase, how ever, has not been examined. It was, therefore, of interest to determi ne whether the addition of guanylin to intact rat colonocytes, or dire ctly to isolated crude colonic membranes, stimulated guanylate cyclase activity. These studies demonstrated that: 1) rat guanylin, in a conc entration-dependent manner, rapidly (within min), but transiently, sti mulated particulate guanylate cyclase activity when added to intact co lonocytes; 2) guanylin also stimulated guanylate cyclase activity when added directly to isolated colonic membranes; and 3) this latter effe ct of guanylin on guanylate cyclase activity was increased by ATP or A DP and markedly accentuated by ATP gamma S. Taken together, these resu lts demonstrate that guanylin rapidly stimulates rat colonic particula te guanylate cyclase activity and, moreover, that this effect can be m odulated by adenine nucleotides. (C) 1994 Academic, Press, Inc.