Kaneko H, Kaunitz J, Taché Y
Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, Digestive Disease Division, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California 90073, USA.
Am J Physiol. 1998 Nov;275(5):G1056-62. doi: 10.1152/ajpgi.1998.275.5.G1056.
Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) and NG-nitro-L-arginine methyl ester (L-NAME). L- but not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.
在乌拉坦麻醉的大鼠中，研究了向中缝苍白核（Rpa）注射海藻酸诱导胃保护作用的外周机制。测量了向Rpa注射海藻酸（25 pg）后胃黏膜血流量（GMBF）、胃酸分泌以及由胃内注射乙醇（60%）诱导的胃损伤情况。海藻酸使乙醇诱导的胃损伤减少了57%。迷走神经切断术、辣椒素去传入神经作用以及静脉注射降钙素基因相关肽（CGRP）拮抗剂CGRP-（8-37）和NG-硝基-L-精氨酸甲酯（L-NAME）可阻断这种保护作用。L-精氨酸而非D-精氨酸可逆转L-NAME的作用。与注射到其他部位不同，向Rpa注射海藻酸可增加基础GMBF，但不影响胃酸分泌。吲哚美辛可揭示出海藻酸对胃酸分泌的反应。这些结果表明，以不刺激胃酸分泌的剂量向Rpa注射海藻酸（由于前列腺素的抑制作用），通过迷走神经依赖激活辣椒素敏感传入神经中所含的CGRP以及一氧化氮介导的胃血管舒张机制，对乙醇诱导的胃损伤具有保护作用。
