Neurohumoral control of ileal electrolyte transport. I. Bombesin and related peptides

The tetradecapeptide bombesin caused a transient increase in transepithelial potential difference and short-circuit current (lsc) when added to the medium bathing the serosal surface of guinea-pig or rat ileal mucosa mounted in vitro in Ussing chambers. Bombesin added to the mucosal bathing medium was ineffective. Bombesin caused a maximal increase of 66 μA/cm² in lsc. A half-maximal increase was obtained with 4.5 x 10^-9 M bombesin. Ranatensin and gastrin-releasing peptide, two naturally occurring peptides with similar sequences to bombesin, also produced large increases in lsc. After addition of bombesin, subsequent additions of peptide exhibited desensitization. Cross-desensitization occurred between bombesin and other similar peptides such as ranatensin, but not with the peptides substance P and neurotensin or with serotonin which also stimulated lsc. Bombesin-induced desensitization was reversible. The effect of bombesin was not blocked by atropine, indomethacin, diphenhydramine, etorphine, somatostatin, epinephrine, tetrodotoxin or verapamil. Replacement of Cl and HCO₃ with gluconate or SO₄ in the Ringer's solution only slightly reduced the effect of bombesin in the guinea pig, but greatly reduced it in the rat. Replacement of Na with choline reduced the action of bombesin substantially in the guinea pig. A combination of a maximally effective concentration of bombesin with prostaglandin E₁ and theophylline only produced a total increment in lsc equal to that produced by bombesin alone. The results suggest that bombesin stimulates active anion secretion by acting on a specific bombesin receptor localized on the serosal surface of ileal epithelial cells.