Pancreatic polypeptie (PP) is released from the pancreas in response to vagal stimulation. Amongst other effects, PP has been reported to inhibit pancreatic exocrine function. Apart from any potential physiological role, such inhibition could have important consequences for in vitro studies of pancreatic function employing acetylcholine as a stimulus. We have therefore tested the effect of bovine PP on two in vitro pancreatic preparations: the incubated, uncinate pancreas of young rats and the perfused cat pancreas. In the former, PP (10(-10)-10(-8)M) had little or no effect on enzyme discharge or45Ca efflux under basal conditions or during stimulation with caerulein, CCK-PZ or acetylcholine. In the perfused cat pancreas, similar concentrations of PP were also without effect on fluid secretion evoked by secretin infusion, or enzyme discharge evoked by CCK-PZ injection or infusion. We conclude that bovine PP has no direct effects on the cellular mechanisms responsible for pancreatic electrolyte secretion or enzyme discharge in the species studied.
Acetylcholine/pharmacology ; Amylases/secretion* ; Animal ; Caerulein/pharmacology ; Calcium/metabolism* ; Cats ; Cholecystokinin/pharmacology ; Electrolytes/secretion* ; In Vitro ; Pancreas/drug effects ; Pancreas/metabolism* ; Pancreatic Polypeptide/pharmacology* ; Perfusion ; Rats ; Secretin/pharmacology

An enhanced formation of nitric oxide(NO), due to the induction of inducible nitric oxide synthase(iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 microgram/kg). Group III received injections of N(G)-nitro-L-arginine methyl este(L-NAME) (30 mg/kg) with cerulein. Group IV received L-arginine(250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury.
Amylases/blood ; Animals ; Arginine/pharmacology ; Blotting, Western ; Caerulein/*pharmacology ; Enzyme Inhibitors/pharmacology ; Inflammation ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Necrosis ; Nitric Oxide/metabolism/*physiology ; Nitric-Oxide Synthase/metabolism ; Pancreatitis/*chemically induced/*metabolism ; Rats ; Rats, Sprague-Dawley