A selective orexin-1 receptor antagonist, SB334867, blocks 2-DG-induced gastric acid secretion in rats
A selective orexin-1 receptor antagonist, SB334867, blocks 2-DG-induced gastric acid secretion in rats
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DOI：
10.1016/j.neulet.2004.11.043
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发表时间：
2005-03
影响因子：
2.5
通讯作者：
Hiroto Yamada;N. Takahashi;S. Tanno;Miho Nagamine;K. Takakusaki;T. Okumura
中科院分区：
文献类型：
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作者：
Hiroto Yamada;N. Takahashi;S. Tanno;Miho Nagamine;K. Takakusaki;T. Okumura
我们先前已经证明脑池内食欲素-A通过迷走神经有力地刺激胃酸分泌。考虑到它对进食的刺激作用，我们假设orexin-A是头相胃分泌的候选介质。也有人认为中枢食欲素A对酸的刺激可能是由脑中的食欲素1受体（OX 1 R）介导的。在本研究中，我们试图阐明大脑中内源性释放的食欲素-A是否确实在胃分泌中发挥生理作用。为了解决这个问题，在大鼠中检查了OX 1 R拮抗剂对胃酸分泌的影响。SB 334867，一种特异性OX 1 R拮抗剂，腹腔内给药本身并不改变幽门结扎清醒大鼠的胃酸分泌。SB 334867以10 mg/kg的剂量预处理完全阻断脑池内食欲素-A而不是促甲状腺素释放激素刺激的酸输出，表明SB 334867特异性阻断食欲素-A在脑中的作用。腹腔注射SB 334867可显著阻断2-脱氧-D-葡萄糖（2-DG）诱导的胃酸分泌刺激。这些结果表明，内源性释放的食欲素-A在大脑中起着至关重要的作用，在中枢调节胃分泌。由于2-DG作为饥饿状态诱导中枢葡萄糖匮乏，本研究进一步支持了食欲素-A可能是触发头相胃酸分泌的重要分子的推测。
We have previously demonstrated that intracisternal orexin-A potently stimulated gastric acid secretion through the vagus nerve. Considering its stimulatory action on feeding, we hypothesized that orexin-A is a candidate mediator of cephalic phase gastric secretion. It has also been suggested that the stimulation of acid by central orexin-A may be mediated by orexin 1 receptor (OX1R) in the brain. In the present study, we tried to clarify whether endogenously released orexin-A in the brain indeed plays a physiological role in gastric secretion. To address the question, the effects of OX1R antagonist on gastric acid secretion was examined in rats. Intraperitoneal administration of SB334867, a specific OX1R antagonist, by itself did not change gastric acid secretion in pylorus-ligated conscious rats. Pretreatment with SB334867 in a dose of 10mg/kg completely blocked the stimulated acid output by intracisternal orexin-A but not thyrotropin-releasing hormone, suggesting that SB334867 specifically blocked the action of orexin-A in the brain. 2-Deoxy-d-glucose (2-DG)-induced stimulation of gastric acid output was significantly blocked by pretreatment with intraperitoneal administration of SB334867. These results suggest that endogenously released orexin-A in the brain plays a vital role in central regulation of gastric secretion. Since 2-DG induces central glucoprivation as a hunger state, the present study furthermore supports the speculation that orexin-A may be an important molecule that triggers the cephalic phase gastric acid secretion.