Regulation of colonic ion transport by GRP .1. GRP stimulates transepithelial K and Na secretion

Regulation of electrolyte transport across porcine distal colon epithelium by gastrin-releasing peptide (GRP) was examined using mucosal sheets mounted in Ussing chambers. Serosal GRP produced a biphasic response consisting of a transient increase in short-circuit current (I-sc) followed by a long-lasting decrease. Indomethacin and tetrodotoxin inhibited the I-sc increase without affecting the secondary decrease. Addition of GRP to the mucosal solution produced a decrease in I-sc similar to that observed with serosal treatment, but no transient increase in I-sc was observed. GRP and bombesin (50% effective concentrations of 26 and 30 nM, respectively) were more effective than neuromedin B in decreasing the I-sc, and the GRP receptor antagonist [D-Phe(6)]bombesin(6-13)-O-methyl produced a sixfold dextral shift in the GRP concentration-response relationship. The GRP-stimulated decrease was reduced in the absence of Cl and by serosal bumetanide. Flux measurements showed that GRP increased Rb and Na secretion while having no effect on transepithelial Cl transport. Phosphoinositide turnover was increased by GRP, suggesting that the ion transport changes may be mediated by intracellular Ca concentration. The results of this study demonstrate that GRP stimulates K and Na secretion across the porcine distal colon epithelium and that these processes are dependent, in part, on a bumetanide-sensitive transport pathway located in the basolateral membrane.