Regulation of intestinal Cl- and HCO3- secretion by uroguanylin

Uroguanylin is an intestinal peptide hormone that may regulate epithelial ion transport by activating a receptor guanylyl cyclase on the luminal surface of the intestine. In this study, we examined the action of uroguanylin on anion transport in different segments of freshly excised mouse intestine, using voltage-clamped Ussing chambers. Uroguanylin induced larger increases in short-circuit current (I sc) in proximal duodenum and cecum compared with jejunum, ileum, and distal colon. The acidification of the lumen of the proximal duodenum (pH 5.0–5.5) enhanced the stimulatory action of uroguanylin. In physiological Ringer solution, a significant fraction of theI sc stimulated by uroguanylin was insensitive to bumetanide and dependent on HCO 3 − in the bathing medium. Experiments using pH-stat titration revealed that uroguanylin stimulates serosal-to-luminal HCO 3 − secretion ( J s → l HCO 3 − ) together with a larger increase inI sc. Both J s → l HCO 3 − and I sc were significantly augmented when luminal p...