Uroguanylin: Cloning of preprouroguanylin cDNA, mRNA expression in the intestine and heart and isolation of uroguanylin and prouroguanylin from plasma

Uroguanylin is a small peptide isolated from opossum urine that activates membrane guanylate cyclases. We report the isolation by molecular cloning of cDNAs encoding the 109 amino acid preprouroguanylin containing the active uroguanylin peptide at its C-terminus. Preprouroguanylin mRNAs of 1.2 kb were detected throughout the small and large intestine and in the atria and ventricles of heart, but not in kidney, stomach or liver. Transfection of COS-1 cells with the uroguanylin cDNA resulted in prouroguanylin secretion. Both uroguanylin and prouroguanylin were isolated from opossum plasma. Thus, uroguanylin is made by the intestine and heart and circulates as a bioactive form of uroguanylin and the inactive prouroguanylin.