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 (I_sc) was 152% (serosal GRP) and 49% (mucosal GRP) greater than control PGE₂ responses alone. Serosal, but not mucosal, GRP also enhanced the I_sc response to vasoactivc 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 I_sc by 35%, whereas mucosal peptide lengthened the time to maximum I_sc by 68%. These results suggest that GRP acts as a modulator of PG action on electrolyte transport in the distal colon.