Tebbe Johannes J, Mronga Silke, Schäfer Martin K-H, Rüter Jens, Kobelt Peter, Mönnikes Hubert
Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps Universität Marburg, 35033 Marburg, Germany.
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1075-83. doi: 10.1152/ajpgi.00125.2003. Epub 2003 Jul 10.
Neuropeptide Y (NPY) neuronal projections from the arcuate nucleus (ARC) have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus (PVN) as part of the ARC-PVN axis. The existence of a positive feedback loop involving CRF receptors in the PVN has been suggested. Exogenous NPY and CRF in the PVN have been shown to inhibit gastric acid secretion. Recently, we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via vagal pathways. To what extent NPY- and CRF-mediated mechanisms in the PVN contribute to the CNS modulation of gastric acid secretion is still an open question. In the present study, we performed consecutive bilateral microinjections of antagonists to NPY receptor subtypes Y1 and Y2 and to CRF1/2 receptors in the PVN and of the excitatory amino acid kainate in the ARC to assess the role of NPY- and CRF-mediated mechanisms in the kainate-induced effects on gastric acid secretion. Gastric acid secretion was measured at the basal condition and during pentagastrin (16 microg/kg body wt) stimulation. Microinjection of vehicle in the PVN and kainate in the ARC decreased gastric acid secretion. Microinjection of the specific NPY-Y1 receptor antagonist BIBP-3226 (200 pmol) and the nonspecific CRF1/2 antagonist astressin (30 pmol) in the PVN abolished the inhibitory effect of neuronal activation in the ARC by kainate on gastric acid secretion. The CRF antagonist astressin was more effective. Pretreatment with the NPY-Y2 receptor antagonist BIIE-0246 (120 pmol) in the PVN had no significant effect. Our results indicate that activation of neurons in the ARC inhibits gastric acid secretion via CRF1/2 and NPY-Y1 receptor-mediated pathways in the PVN.
弓状核（ARC）的神经肽Y（NPY）神经元投射被认为以室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）阳性神经元为靶点，作为ARC-PVN轴的一部分。有人提出在PVN中存在一个涉及CRF受体的正反馈回路。PVN中的外源性NPY和CRF已被证明可抑制胃酸分泌。最近，我们已经证明ARC神经元的激活通过迷走神经通路抑制胃酸分泌。PVN中NPY和CRF介导的机制在多大程度上参与中枢神经系统对胃酸分泌的调节仍是一个悬而未决的问题。在本研究中，我们在PVN中连续双侧微量注射NPY受体亚型Y1和Y2以及CRF1/2受体的拮抗剂，并在ARC中注射兴奋性氨基酸海藻酸，以评估NPY和CRF介导的机制在海藻酸诱导的胃酸分泌效应中的作用。在基础状态和五肽胃泌素（16微克/千克体重）刺激期间测量胃酸分泌。在PVN中注射溶剂和在ARC中注射海藻酸可降低胃酸分泌。在PVN中微量注射特异性NPY-Y1受体拮抗剂BIBP-3226（200皮摩尔）和非特异性CRF1/2拮抗剂阿斯特辛（30皮摩尔）可消除海藻酸对ARC神经元激活对胃酸分泌的抑制作用。CRF拮抗剂阿斯特辛更有效。在PVN中用NPY-Y2受体拮抗剂BIIE-0246（120皮摩尔）预处理没有显著影响。我们的结果表明，ARC中神经元的激活通过PVN中CRF1/2和NPY-Y1受体介导的途径抑制胃酸分泌。
