Effect of nitric oxide on the somatostatinergic system in the rat exocrinepancreas

Nitric oxide (NO) and somatostatin (SS) are two important mediators of the exocrine and endocrine pancreas, exerting opposite effects on this organ. T here is strong evidence suggesting an interaction between pancreatic NO and SS. The aim of this study was to determine whether L-arginine (L-Arg), the substrate for NO synthase (NOS), and N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, regulate pancreatic somatostatin-like immunorea ctivity (SSLI) content and the SS mechanism of action in pancreatic acinar cell membranes. L-Arg (150 mg/kg, intraperitoneally (i.p.)), L-NAME (50 mg/ kg, i.p.) or L-NAME plus L-Arg were injected twice daily at 8 h intervals f or 8 days. L-Arg decreased pancreatic SSLI content as well as the number of SS receptors in pancreatic acinar cell membranes whereas L-NAME increased both parameters. The stable SS analogue SMS 201-995 induced a significantly lower inhibition of forskolin-stimulated adenylyl cyclase activity in panc reatic acinar cell membranes from L-Arg-treated rats whereas an increased i nhibition was observed in pancreatic acinar membranes from L-NAME-treated r ats. These results indicate that the NO system may contribute to the regula tion of the pancreatic somatostatinergic system. (C) 1999 Elsevier Science B.V. All rights reserved.