Increasing numbers of peptide hormones appear to stimulate pancreatic enzyme secretion via vagal cholinergic pathways. Studies in rats indicated that cholecystokinin at physiologic levels stimulates pancreatic secretion via a capsaicin-sensitive afferent vagal pathway. Similar cholinergic dependency was observed in other stimulatory peptides such as neurotensin and adenylate cyclase activating polypeptide. Recent human studies further confirmed the existence of a feedback mechanism between cholecystokinin release and pancreatico-biliary secretion. Cholecystokinin receptor blockade resulted in enhancement of postprandial plasma cholecystokinin levels but had no effect on basal plasma cholecystokinin levels. Under fasting conditions, however, cholecystokinin receptor blockade increased cholecystokinin synthesis but not its release. Further studies in rats indicated that dietary problems in the intenstine modulate feedback regulation of cholecystokinin release by luminal trypsin inhibitors. Endocrine and exocrine pancreatic interaction has important functional and clinical significance. Studies in rats showed that insulin exerted a direct potentiating effect on pancreatic acinar cells by increasing Na+, K+-ATPase activity. In isolated rat pancreas, somatostatin-enhanced arginine evoked pancreatic secretion by inhibiting the release of glucagon under hypoglycemic conditions. However, in euglycemic conditions somatostatin inhibited pancreatic secretion by acting at a central vagal site. Two separate laboratories provided convincing evidence that NO (nitric oxide), produced by NO synthase mediated he stimulation by carbachol of cyclic GMP formation, which in turn evoked Ca2+influx in pancreatic acinar cells. The activity of NO synthase was regulated by internal Ca2+stores. This provides a novel mechanism to explain Ca2+transport in pancreatic acinar cells. In the field of pancreatic growth and proliferation, the demonstration that concomitant expression of high levels of fibroblast growth factors (FGFs) and FGF receptors in pancreatic cancer cells was associated with advanced clinical stages and poor prognosis suggests that these growth factors may contribute to progression of the pancreatic cancer by allowing excessive autocrine and paracrine growth stimulation.
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