Regulation of colonic ion transport by GRP. II. GRP modulates the epithelial response to PGE2

The purpose of this study was to examine the potential modulatory effects of gastrin-releasing peptide (GRP) on prostaglandin (PG) E2-stimulated electrolyte transport across the distal colon epithelium. In an earlier study, PGE2 was shown to reduce net Cl absorption without altering the serosal-to-mucosal unidirectional Cl flux in porcine distal colon (19). In the present study, tissues were pretreated with serosal or mucosal GRP and subsequently stimulated with PGE2. The resulting increase in short-circuit current (ISC) was 152% (serosal GRP) and 49% (mucosal GRP) greater than control PGE2 responses alone. Serosal, but not mucosal, GRP also enhanced the ISC response to vasoactive intestinal peptide. On the basis of flux measurements, the combined effects of serosal GRP and PGE2 resulted in the activation of a transcellular pathway for Cl secretion, which was not activated by either mediator alone. The time course of the PGE2 response was also affected by GRP. Serosal GRP shortened the time to maximum ISC by 35%, whereas mucosal peptide lengthened the time to maximum ISC by 68% These results suggest that GRP acts as a modulator of PG action on electrolyte transport in the distal colon.