Abstract
The role of nitric oxide (NO) in the regulation of exocrine secretion was investigated in isolated rat pancreatic acini. NO synthase activity was detected in the extract of acini and purified by ion-exchange and 2′, 5′-ADP agarose chromatographies. Enzyme activity was determined by conversion of 3H-arginine to 3H-citrulline, by measurement of nitrite (a breakdown product of NO) and by generation of cyclic GMP. Treatment of acini with L-arginine increased nitrite as well as cyclic GMP and amylase release, which were prevented by the nitric oxide synthase inhibitors N-monomethyl-arginine [NMMA] and N G-nitro-L-arginine [NNA]. These nitric oxide inhibitors also blocked carbachol-induced amylase release as well as elevation of acinar cell cyclic GMP. NNA was a potent inhibitor of carbamylcholine-induced amylase release (est. K i=2.2 uM). Nitric oxide apparently participates significantly in the overall control of pancreatic acinar cell secretory function.
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