Yamaguchi N, Fukushima Y
Groupe de recherche sur le système nerveux autonome, Faculté de Pharmacie, Université de Montréal, QC, Canada.
Can J Physiol Pharmacol. 1998 Jul-Aug;76(7-8):788-97. doi: 10.1139/cjpp-76-7-8-788.
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.
本研究旨在探讨垂体腺苷酸环化酶激活多肽（PACAP）是否能够改变麻醉犬胰腺神经刺激引起的去甲肾上腺素（NE）释放。采用高效液相色谱法测定主动脉和胰十二指肠上静脉（SPD）血中的血浆儿茶酚胺浓度。用电磁流量计测量SPD静脉血流量。在SPD动脉水平以不同频率直接刺激胰腺神经1分钟（2毫秒，12伏）。通过SPD动脉将不同剂量的PACAP1-27（PACAP27）局部注入胰腺。神经刺激以频率依赖性方式显著增加SPD静脉NE浓度及其从胰腺的输出量。单独使用PACAP27时，在任何测试剂量下局部给予PACAP27后，SPD静脉NE浓度及其输出量均无显著变化。然而，在存在PACAP27的情况下，2赫兹神经刺激引起的NE浓度及其输出量的净增加以剂量依赖性方式显著增强。因此，PACAP27对神经刺激增强的NE反应显著大于单独接受PACAP27或刺激的组。神经胺摄取抑制剂地昔帕明几乎消除了酪胺局部给药引起的NE浓度及其输出量的增加。然而，PACAP27并未减弱对酪胺的NE反应。结果表明，PACAP27增强了胰腺中刺激诱导的NE释放，且PACAP27的这种促进作用并非源于对神经胺摄取机制的抑制。该研究表明，PACAP受体介导的机制可能直接或间接参与体内犬胰腺神经NE释放的局部调节。
