Role of VIP in local control of secretion

Abstract. Vasoactive intestinal peptide (VIP) is a potent stimulant of duodenal HCO3− secretion and may, like prostaglandins, have a stimulatory role in the local duodenal HCO3− response to luminal HCl. Using a proximal duodenal loop in conscious rats, we examined the local luminal release of HCO3−. VIP and prostaglandin (PG) E2 in response to increasing concentrations of HCl (0.01–150 mmol l−1), perfused for 5 min at 60‐min intervals. HCO3− and PGE2 were detected in all basal saline perfusate effluents, and were increased in a concentration‐dependent manner by all acid concentrations tested. VIP was increased in a concentration dependent manner from pH 3. Exogenous VIP did not affect the basal luminal output of PGE2, or vice versa. Inhibition of prostaglandin synthesis by indomethacin augmented the HCl‐stimulated luminal release of VIP, as well as the HCO3−response to exogenous VIP. The results are in agreement with previous studies, demonstrating that PGE2 is an important regulator of the duodenal HCO3− response to HCl in the rat. In addition, prostaglandins may negatively modulate the release of VIP from local VIPergic neurones, as well as the HCO3− secretagogue effect of VIP. Released VIP may contribute to the HCO3− response at pH ≤ 3.