Kaneko H, Mitsuma T, Nagai H, Mori S, Iyo T, Kusugami K, Tache Y
Fourth Department of Internal Medicine, Aichi Medical University, Aichi 480-1195, Japan.
Am J Physiol. 1998 Jun;274(6):R1783-8. doi: 10.1152/ajpregu.1998.274.6.R1783.
Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP1 receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40-72% and rat alpha-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP1 receptor antagonist CGRP-(8-37) (9.6-19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal alpha-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or NG-nitro-L-arginine methyl ester (L-NAME) prevented AM protective action. L-Arginine but not D-arginine blocked L-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms.
肾上腺髓质素（AM）属于降钙素基因相关肽（CGRP）家族，可与AM和CGRP1受体相互作用。大鼠脑中存在特异性AM受体和免疫反应性。在清醒的Wistar大鼠中研究了脑池内注射大鼠AM对乙醇诱导的胃损伤的影响。在胃内注射70%乙醇前20分钟，在短暂麻醉下将该肽脑池内或静脉内注射。乙醇注射1小时后测定胃体损伤情况。脑池内注射AM（75、150和300皮摩尔）剂量依赖性地抑制乙醇诱导的胃损伤达40%-72%，而大鼠α-CGRP（150皮摩尔脑池内注射）抑制率达76%。静脉注射AM（300皮摩尔）无作用。CGRP1受体拮抗剂CGRP-(8-37)（9.6-19.2纳摩尔脑池内注射）剂量依赖性地抑制脑池内α-CGRP的保护作用，但不抑制AM的保护作用。膈下迷走神经切断术以及外周注射阿托品、吲哚美辛或NG-硝基-L-精氨酸甲酯（L-NAME）可阻止AM的保护作用。L-精氨酸而非D-精氨酸可阻断L-NAME的作用。这些数据表明，AM和CGRP均在脑内发挥作用，通过与其特异性受体相互作用来预防乙醇诱导的胃损伤。AM的作用可能涉及迷走胆碱能依赖性对前列腺素和一氧化氮保护机制的调节。
