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 secr etion. Upon stimulating pancreatic acinar cells with cholecystokinin- pancreozymin (CCK-PZ), NO formation has been shown to be associated wi th increased levels of cGMP (See et al., 1995). To elucidate the signa ling pathway of VIP-induced enzyme secretion, we investigated the NO a nd cGMP synthesis steps as potential steps where two signal pathways t riggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by trea tment with VIP has no relationship with NOS activity and cGMP level. T his conclusion was derived from the following findings that VIP treatm ent of rat pancreatic tissue increased amylase release as well as prot ein 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 confi rmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases e nzyme secretion in rat pancreatic tissue, but the two hormones are dif ferent in their mode of action. Together the results suggest that sign aling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-i nduced pathway.