Department of Pharmacology, Tohoku Pharmaceutical University, 4–4–1 Komatsushima, Aoba-ku, Sendai 981–8558, Japan.
Biol Pharm Bull. 2012;35(1):91-7. doi: 10.1248/bpb.35.91.
Exercise necessitates a large supply of O(2) and nutrients and rapid removal of CO(2) and waste products. Histamine is a regulator of the microcirculation (which performs these exchanges), suggesting a possible involvement of histamine in exercise. Histamine is released from either mast cells or non-mast cells. In the latter, histamine is newly formed via the induction of histidine decarboxylase (HDC) in response to an appropriate stimulus, and it is released without being stored. Here, in mice, we examined the role of histamine or HDC induction in exercise. Prolonged walking (PW) (in a cylindrical cage turned electrically) increased HDC mRNA and HDC activity in quadriceps femoris muscles. Mice given a histamine H1-receptor antagonist [fexofenadine (peripherally acting) or pyrilamine (peripherally and centrally acting)] or an irreversible HDC inhibitor (α-fluoromethylhistidine) displayed less PW endurance than control mice. Ranitidine (H2-receptor antagonist) tended to reduce endurance. Other histamine-receptor (H3 and H4) antagonists had no significant effects on endurance. Mice deficient in HDC or histamine H1-receptors displayed markedly less endurance than control mice, and HDC activity in the quadriceps femoris of H1-deficient mice was rapidly elevated by PW. Fexofenadine significantly reduced the muscle levels of nitric oxide (NO) metabolites and glycogen after PW. The results support the ideas that (i) histamine is involved in protecting against exercise-induced fatigue or exhaustion, (ii) histamine exerts its protective effect via H1 receptors and the ensuing production of NO in skeletal muscle, and (iii) histamine is provided, at least in part, by HDC induction in skeletal muscles during prolonged exercise.
运动需要大量的 O(2) 和营养物质，并迅速清除 CO(2) 和废物。组织胺是微循环的调节剂（执行这些交换），这表明组织胺可能参与了运动。组织胺可以从肥大细胞或非肥大细胞中释放出来。在后一种情况下，组织胺是通过诱导组氨酸脱羧酶（HDC）形成的，这是对适当刺激的反应，并且在没有储存的情况下释放。在这里，在小鼠中，我们研究了组织胺或 HDC 诱导在运动中的作用。长时间行走（PW）（在电动旋转的圆柱形笼子中）增加了股四头肌中的 HDC mRNA 和 HDC 活性。给予组织胺 H1 受体拮抗剂[非索非那定（外周作用）或苯海拉明（外周和中枢作用）]或不可逆的 HDC 抑制剂（α-氟甲基组氨酸）的小鼠比对照小鼠显示出较少的 PW 耐力。雷尼替丁（H2 受体拮抗剂）倾向于降低耐力。其他组织胺受体（H3 和 H4）拮抗剂对耐力没有显著影响。缺乏 HDC 或组织胺 H1 受体的小鼠表现出明显较少的耐力，并且 H1 缺陷小鼠股四头肌中的 HDC 活性在 PW 后迅速升高。非索非那定显著降低了 PW 后肌肉中一氧化氮（NO）代谢物和糖原的水平。这些结果支持了以下观点：（i）组织胺参与保护免受运动引起的疲劳或衰竭，（ii）组织胺通过 H1 受体及其随后在骨骼肌中产生的 NO 发挥其保护作用，以及（iii）组织胺至少部分由长时间运动中骨骼肌中的 HDC 诱导提供。
