Regulatory Effects of Nitric Oxide (NO) on Pancreatic Exocrine Secretion

Han, Yu Mi; Min, Bon Hong; Park, In Sun

Abstract

Recently nitric oxide (NO) is known as a bioactive molecule modulating secretory activity in various glandular tissues. Previously we have localized bNOS, a neuronal isoform of nitric oxide synthase, in the pancreatic tissue, particularly in the pancreatic islet of Langerhans and in the neurons of intrapancreatic ganglia. It implies that NO may play the important roles in regulation of pancreatic secretion by transmitting the neuronal signals from autonomic nervous system to endocrine and/or exocrine system of pancreas. We also revealed that NO is involved in regulation of insulin secretion and its synthesis. The present study was designed to elucidate the regulatory effect of NO on the pancreatic exocrine secretion by way of insulo-acinar axis. For the experiment, we observed modification of amylase secretion in the rats treated with N(G)-nitro-L-arginine-methyl ester (NAME), a potent NOS inhibitor. In addition, we observed the expression of clusterin which is known to be a protein associated with cell viability in order to assess the cytotoxic effect of NO. The present study showed that the intra-pancreatic NO is involved in regulation of amylase secretion of pancreatic acinar cells. Amylase immunoreactivity was significantly decreased at 60 and 90 min after NAME injection, although little change was seen during 30 min after treatment. However, the amylase immunoreaction was recovered toward the normal range at 120 min after NAME treatment. In electron-immunolabeling experiment, we observed the secretory granules with higher electron density, but less immunolabeling for amylase at 60~90 min after NAME treatment, while they restored normal feature and labeling density at 120 min. Clusterin expression increased along with the time course of experiment and demonstrated a highest level at 120 min after NAME injection. Taken together, the above results indicate that lowered level of NO induced by NAME treatment reduces amylase secretion of acinar tissue. It implies that increased level of NO in physiological range may stimulate pancreatic exocrine secretion.