PACAP enhances stimulation-induced norepinephrine release in canine pancreas in vivo

The present study was to investigate whether pituitary adenylate cyclase activating polypeptide (PACAP) can modify norepinephrine (NE) release in response to pancreatic nerve stimulation in anesthetized dogs. Plasma catecholamine concentrations in aortic and superior pancreaticoduodenal (SPD) venous blood were determined by a high performance liquid chromatography method. SPD venous blood flow was measured with an electromagnetic flowmeter. Pancreatic nerves were directly stimulated for 1 min (2 ms, 12 V) at various frequencies at the level of the SPD artery. Various doses of PACAP1-27 (PACAP27) were locally infused into the pancreas through the SPD artery. Nerve stimulation significantly increased both SPD venous NE concentration and its output from the pancreas in a frequency-dependent manner. With PACAP27 alone, neither SPD venous NE concentration nor its output changed significantly following the local administration of PACAP27 at any dose tested. In the presence of PACAP27, however, the net increases in NE concentration and its output in response to nerve stimulation at 2 Hz were significantly enhanced in a dose-dependent manner. The enhanced NE responses to nerve stimulation by PACAP27 were thus significantly greater than those obtained from the group receiving either PACAP27 or stimulation alone. Increases in NE concentration and its output induced by local administration of tyramine were virtually abolished by desipramine, a neural amine uptake inhibitor. However, the NE response to tyramine was not diminished by PACAP27. The results indicate that PACAP27 enhances the stimulation-induced NE release in the pancreas, and that this facilitatory effect of PACAP27 does not result from an inhibition of the neural amine uptake mechanism. The study suggests that PACAP receptor-mediated mechanisms may be involved either directly or indirectly in the local modulation of neural NE release in the canine pancreas in vivo.