Krowicki Z K, Hornby P J
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Centre, New Orleans 70112, USA.
Neurogastroenterol Motil. 1996 Dec;8(4):307-17. doi: 10.1111/j.1365-2982.1996.tb00269.x.
Several in vitro models of gastric relaxation have elucidated a role of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in non-adrenergic, non-cholinergic (NANC) vagally mediated gastric relaxation. However, these models do not necessarily mimic the events leading to gastric relaxation in the whole animal. We have recently described a vagally mediated gastric relaxation evoked by micro-injection of substance P (SP) into the nucleus raphe obscurus (NRO). The present study was performed to elucidate whether this CNS-stimulated in vivo gastric relaxation involved acetylcholine, NO and VIP. Atropine (1 mg kg-1 i.v.), reduces both the rapid nadir and sustained gastric relaxation evoked by SP in the NRO, and the residual responses are abolished by NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg kg-1 i.v.), an NO synthase inhibitor. Blockade of NO synthase alone is not sufficient to abolish the effect of SP into the NRO on intragastric pressure. A VIP antagonist, [p-chloro-D-Phe6, Leu17]VIP (32 micrograms i.v.) alone, or with the addition of L-NAME, does not affect the nadir of the gastric relaxation in response to SP microinjected into the NRO; however, both antagonists reduce the CNS-evoked sustained intragastric pressure relaxation. We conclude that, in CNS-evoked gastric relaxation, inhibition of cholinergic pathways is potentially important for both the rapid nadir and sustained gastric relaxation, and both NO and VIP contribute to sustained gastric relaxation.
几种胃舒张的体外模型已经阐明了一氧化氮（NO）和血管活性肠肽（VIP）在非肾上腺素能、非胆碱能（NANC）迷走神经介导的胃舒张中的作用。然而，这些模型不一定能模拟导致全动物胃舒张的事件。我们最近描述了一种通过向中缝隐核（NRO）微量注射P物质（SP）诱发的迷走神经介导的胃舒张。本研究旨在阐明这种中枢神经系统刺激的体内胃舒张是否涉及乙酰胆碱、NO和VIP。静脉注射阿托品（1 mg/kg）可降低SP在NRO中诱发的快速最低点和持续的胃舒张，而剩余反应被NO合酶抑制剂盐酸N-硝基-L-精氨酸甲酯（L-NAME，10 mg/kg静脉注射）消除。单独阻断NO合酶不足以消除向NRO注射SP对胃内压的影响。VIP拮抗剂[p-氯-D-苯丙氨酸6，亮氨酸17]VIP（32微克静脉注射）单独使用或与L-NAME联合使用，并不影响向NRO微量注射SP后胃舒张的最低点；然而，两种拮抗剂都能降低中枢神经系统诱发的持续胃内压舒张。我们得出结论，在中枢神经系统诱发的胃舒张中，胆碱能途径的抑制对于快速最低点和持续的胃舒张都可能很重要，并且NO和VIP都有助于持续的胃舒张。
