Role of VIP in local control of secretion

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 less than or equal to 3.