STRUCTURE AND ACTIVITY OF UROGUANYLIN AND GUANYLIN FROM THE INTESTINEAND URINE OF RATS

Uroguanylin and guanylin are related peptides that activate common gua nylate cyclase signaling molecules in the intestine and kidney. Urogua nylin was isolated from urine and duodenum but was not detected in ext racts from the colon of rats. Guanylin was identified in extracts from small and large intestine but was not detected in urine. Uroguanylin and guanylin have distinct biochemical and chromatographic properties that facilitated the separation, purification, and identification of t hese peptides. Northern assays revealed that mRNA transcripts for urog uanylin were more abundant in small intestine compared with large inte stine, whereas guanylin mRNA levels were greater in large intestine re lative to small intestine. Synthetic rat uroguanylin and guanylin had similar potencies in the activation of receptors in T84 intestinal cel ls. Production of uroguanylin and guanylin in the mucosa of duodenum i s consistent with the postulate that both peptides influence the activ ity of an intracellular guanosine 3',5'-cyclic monophosphate signaling pathway that regulates the transepithelial secretion of chloride and bicarbonate in the intestinal epithelium.