Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat.

The peptide uroguanylin (Ugn) is stored and released as a propeptide (proUgn) by enterochromaffin cells in the intestine, and converted to Ugn and other metabolites in the renal tubules. Both proUgn and Ugn are natriuretic, although the response to proUgn is thought to depend on its conversion to Ugn within nephrons. To assess the efficiency of intrarenal conversion of proUgn to Ugn, we measured urinary Ugn excretion in rats following intravenous infusions of proUgn or Ugn. Infusion of 2 and 10 nmol proUgn/kg body wt increased plasma proUgn concentration from 2.2 ± 0.3 to 5.6 ± 1.3 pmol/ml and to 37 ± 9.6 pmol/ml, respectively. No proUgn was detected in urine before, during, or after proUgn infusions. These two proUgn infusion doses resulted in total Ugn recovery in urine of 162 ± 64 and 206 ± 39 pmol/kg body wt (9 and 2% of the infused amount, respectively). By contrast, the same molar amounts of Ugn resulted in 1,009 ± 477 and 5,352 ± 2,133 pmol/kg body wt of Ugn in urine (recoveries of ∼50%). Unexpectedly, comparisons of natriuretic dose-response curves for each peptide showed proUgn to be about five times more potent than Ugn, despite the relatively modest amount of Ugn generated from infused proUgn. In addition, both peptides were antikaliuretic at low doses, but in this case Ugn showed greater potency than proUgn. These data do not support Ugn as the primary active principle of proUgn for regulation of renal sodium excretion. Instead, an alternative peptide fragment produced from proUgn may be responsible for natriuretic activity in the kidney, whereas Ugn itself may play an antikaliuretic role.