An intestinal factor responsible for the natriuresis elicited by oral salt has long been sought. A candidate pepn'de named uroguanylin was previously isolated from opossum urine and intestinal mucosa. We report here the molecular cloning of cDNAs encoding preprouroguanylin from an opossum colon cDNA library. Sequence analysis of the cDNA clone predicts a protein of 109 aniino acids that starts with a signal peptide domain of 23 residues. The C-terminal portion of the ORF encodes the published uroguanylin sequence. Preprouroguanylin is 35% and 33% identical to rat and human preproguanylins, respectively. When recombinant DNA containing the preprouroguanylin ORF was expressed in COS-1 cells, the inactive prohormone was secreted into the medium. The secreted form of prouroguanylin was activated by chymotrypsin pretreatment. Uroguanyiin and guanylin mRNA expression patterns were compared using Northern analysis. Preprouroguanylin mRNAs of 1.2 kb were detected throughout all of the maior segments of small and large intestine and surprisingly, in the atria and ventricles of heart. Transcripts were not found in kidney, stomach or liver. Preproguanylin mRNAs of 0.8 kb were only detected in the intestine. Interestingly, a reciprocal relationship for uroguanylin and guanylin mRNA expression was apparent in the major intestinal segments, suggesting that these two hormones have complementary functions in the intestine. In conclusion, the production of uroguanylin in the intestine and its existence in urine suggests that uroguanylin links the intestine with the kidney to coordinate renal salt excretion with oral salt intake.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology