NEUROHORMONAL CONTROL OF THE EXOCRINE PANCREAS

Increasing numbers of peptide hormones appear to stimulate pancreatic enzyme secretion via vagal cholinergic pathways. Studies in rats indic ated that cholecystokinin at physiologic levels stimulates pancreatic secretion via a capsaicin-sensitive afferent vagal pathway. Similar ch olinergic dependency was observed in other stimulatory peptides such a s neurotensin and adenylate cyclase activating polypeptide. Recent hum an studies further confirmed the existence of a feedback mechanism bet ween cholecystokinin release and pancreatico-biliary secretion. Cholec ystokinin receptor blockade resulted in enhancement of postprandial pl asma cholecystokinin levels but had no effect on basal plasma cholecys tokinin levels. Under fasting conditions, however, cholecystokinin rec eptor blockade increased cholecystokinin synthesis but not its release . Further studies in rats indicated that dietary problems in the intes tine modulate feedback regulation of cholecystokinin release by lumina l trypsin inhibitors. Endocrine and exocrine pancreatic interaction ha s important functional and clinical significance. Studies in rats show ed that insulin exerted a direct potentiating effect on pancreatic aci nar cells by increasing Na+,K+-ATPase activity. In isolated rat pancre as, somatostatin-enhanced arginine evoked pancreatic secretion by inhi biting 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 med iated the stimulation by carbachol of cyclic GMP formation, which in t urn 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 (FG Fs) and FGF receptors in pancreatic cancer cells was associated with a dvanced clinical stages and poor prognosis suggests that these growth factors may contribute to progression of the pancreatic cancer by allo wing excessive autocrine and paracrine growth stimulation.