Yoneda Masashi, Goto Manabu, Nakamura Kimihide, Yokohama Shiro, Kono Toru, Tanamo Masaya, Shimada Tadahito, Hiraishi Hideyuki
Department of Gastroenterology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan.
Regul Pept. 2005 Nov;131(1-3):74-81. doi: 10.1016/j.regpep.2005.06.010.
Central administration of thyrotropin-releasing hormone (TRH) enhanced pancreatic blood flow in animal models. TRH nerve fibers and receptors are localized in the dorsal vagal complex (DVC), and retrograde tracing techniques have shown that pancreatic vagal nerves arise from the DVC. However, nothing is known about the central sites of action for TRH to elicit the stimulation of pancreatic blood flow. Effect of microinjection of a TRH analog into the DVC on pancreatic blood flow was investigated in urethane-anesthetized rats. After measuring basal flow, a stable TRH analog (RX-77368) was microinjected into the DVC and pancreatic blood flow response was observed for 120 min by laser Doppler flowmetry. Vagotomy of the several portions, or pretreatment with atoropine methyl nitrate or N(G)-nitro-l-arginine-methyl ester was performed. Microinjection of RX-77368 (0.1-10 ng) into the left or right DVC dose-dependently increased pancreatic blood flow. The stimulation of pancreatic blood flow by RX-77368 microinjection was eliminated by the same side of cervical vagotomy as the microinjection site or subdiaphragmatic vagotomy, but not by the other side of cervical vagotomy. The TRH-induced stimulation of pancreatic blood flow was abolished by atropine or N(G)-nitro-l-arginine-methyl ester. These results suggest that TRH acts in the DVC to stimulate pancreatic blood flow through vagal-cholinergic and nitric oxide dependent pathways, indicating that neuropeptides may act in the specific brain nuclei to regulate pancreatic function.
在动物模型中，促甲状腺激素释放激素（TRH）的中枢给药可增强胰腺血流。TRH神经纤维和受体定位于迷走神经背侧复合体（DVC），逆行追踪技术表明胰腺迷走神经起源于DVC。然而，关于TRH引起胰腺血流刺激的中枢作用位点尚不清楚。在乌拉坦麻醉的大鼠中，研究了向DVC微量注射TRH类似物对胰腺血流的影响。在测量基础血流后，将稳定的TRH类似物（RX-77368）微量注射到DVC中，并通过激光多普勒血流仪观察120分钟的胰腺血流反应。进行了几个部位的迷走神经切断术，或用硝酸甲基阿托品或N（G）-硝基-L-精氨酸甲酯进行预处理。将RX-77368（0.1-10 ng）微量注射到左侧或右侧DVC中可剂量依赖性地增加胰腺血流。与微量注射部位同侧的颈迷走神经切断术或膈下迷走神经切断术可消除RX-77368微量注射对胰腺血流的刺激，但另一侧的颈迷走神经切断术则不能。阿托品或N（G）-硝基-L-精氨酸甲酯可消除TRH诱导的胰腺血流刺激。这些结果表明，TRH在DVC中起作用，通过迷走胆碱能和一氧化氮依赖性途径刺激胰腺血流，表明神经肽可能在特定脑核中起作用以调节胰腺功能。
