Vasoactive intestinal peptide (VIP)-induced enzyme secretion in rat pancreatic tissue is not associated with activation of nitric oxide synthase (NOS) and increase in cyclic GMP level

Nitric oxide (NO) is thought to be a second messenger involved in secretion. Upon stimulating pancreatic acinar cells with cholecystokinin- pancreozymin (CCK-PZ), NO formation has been shown to be associated with increased levels of cGMP (Seoet al., 1995). To elucidate the signaling pathway of VIP-induced enzyme secretion, we investigated the NO and cGMP synthesis steps as potential steps where two signal pathways triggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by treatment with VIP has no relationship with NOS activity and cGMP level. This conclusion was derived from the following findings that VIP treatment of rat pancreatic tissue increased amylase release as well as protein output in a dose- and time-dependent manner, whereas NOS activity and cGMP synthesis were not affected by VIP treatment as monitored by NOS activity assay and determining cGMP level, which was further confirmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases enzyme secretion in rat pancreatic tissue, but the two hormones are different in their mode of action. Together the results suggest that signaling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-induced pathway.