DETECTION AND ROLE OF THE FREE RADICAL NITRIC OXIDE IN THE EXOCRINE PANCREAS Summary of PhD Thesis

2002 2 Summary The free radical nitric oxide (NO) has several functions in various tissues. NO is well distributed in the gastrointestinal system including the pancreas and thought to be involved in the regulation of blood flow, motility and secretion. Although morphological reports provide evidence for the intrapancreatic production of NO, much less is known about the direct actions of NO exerted on the exocrine pancreatic tissues. Neuronal nitric oxide synthase (nNOS) was both enzyme-and immunohistochemically localized in the porcine and rat pancreas. Reduced nicotinamide-adenine-dinucleotide-phosphate (NADPH) diaphorase (NADPHd) reactivity (R) and/or nNOS immunoreactivity (IR) was identified in the pancreatic ganglion cells and in nerve fibers next to acini and blood vessels. NADPHd R was also displayed by the porcine vascular endothelium, whereas the islet cells and the rat ductal epithelium occasionally showed nNOS IR. The distribution of nNOS in the neuronal and especially in the non-neuronal tissues showed age-related changes with increased contents of nNOS in the adult and ageing rat pancreas. In order to demonstrate the direct actions of NO on in vitro rat preparations, we studied the effects of the NO donor sodium nitroprusside (SNP), the NOS substrate L-arginine (L-Arg), the NOS inhibitor N G-nitro-L-arginine (LNNA) and the cyclic GMP (cGMP) analogue 8-bromo cGMP (8-Br cGMP) on basal and stimulated amylase secretion in isolated rat pancreatic segments. Stimulation was achieved by either acetylcholine (ACh) or electrical field stimulation (EFS). The changes in intracellullar free calcium concentration (