NO/cGMP pathway is involved in exocrine secretion from rat pancreatic acinar cells

The enzyme responsible for the synthesis of nitric oxide (NO) from L-argini ne in mammalian tissues is known as nitric oxide synthase (NOS) (EC.1.14.13 .39). In the present study, the role of NO in the regulation of exocrine se cretion was investigated in rat pancreatic acinar cells. Treatment of rat p ancreatic acinar cells with cholecystokinin-octapeptide (CCK-OP) resulted i n an increase in the arginine conversion to citrulline, the amount of NOx, the release of amylase, and the level of cGMP. Especially, CCK-OP-stimulate d increase of arginine to citrulline transformation, the amount of NO, and cGMP level were completely counteracted by the inhibitor of NOS, NG-monomet hyl-L-arginine (MMA), by contrast, that of amylase release was partially re duced. Furthermore, MMA-induced decrease of NOS activity and amylase releas e showed dose-dependent pattern. The data on the time course of CCK-OP-indu ced citrulline formation and cGMP rise indicate that NOS and guanylate cycl ase were activated by treatment of CCK-OP. However, the mechanism of agonis t-stimulated guanylate cyclase activation in acinar cells remains unknown. Therefore, activation of NOS is one of the early events in receptor-mediate d cascade of reactions in pancreatic acinar cells and NO, not completely, b ut partially mediate pancreatic enzyme exocrine secretion.