Moriya T, Ishida Y, Nakamura H, Asari T, Murai A, Ohizumi Y
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Eur J Pharmacol. 1998 May 29;350(1):59-65. doi: 10.1016/s0014-2999(98)00225-8.
We found that zooxanthellatoxin-B from a symbiotic marine alga, Symbiodinium sp., caused a concentration-dependent contraction of the rabbit isolated aorta at concentrations of 10(-7)-10(-5) M. Verapamil (10(-6) M) and mefenamic acid (10(-5) M) significantly attenuated the contractile response to zooxanthellatoxin-B at lower concentrations (10(-7)-10(-6) M) but not at higher concentrations (3 X 10(-6)-10(-5) M). The response to zooxanthellatoxin-B was partly inhibited by phentolamine (10(-6) M), whereas it was potentiated by ouabain (10(-5) M). Tetrodotoxin (10(-6) M), methysergide (10(-6) M), chlorpheniramine (10(-6) M) or indomethacin (3 X 10(-6) M), however, did not affect it. The zooxanthellatoxin-B-induced contraction was abolished by incubation in Ca2+-free solution. The contractile response increased in a concentration-dependent fashion with Ca2+ (0.03 and 10 mM) or Sr2 + (0.10 and 10 mM). After treatment with verapamil (10(-6) or 5 X 10(-6) M), the concentration-contractile response curves for Ca2+ and Sr2+ in the presence of zooxanthellatoxin-B were shifted to the right in parallel. MgCl2 (10 mM) shifted the concentration-response curve for Ca2+ more markedly than did verapamil. Zooxanthellatoxin-B increased tissue Na+ and reduced tissue K+ contents in the aorta, suggesting that zooxanthellatoxin-B increases Na+ and K+ permeability across the plasma membrane. These results suggest that the zooxanthellatoxin-B-induced contraction of the aorta is caused mainly by a direct action on smooth muscle, i.e., an increase in Ca2+ permeability that occurs at least partly through voltage-sensitive Ca2+ channels as well as through nonselective cation channels in the cell membrane of smooth muscle.
我们发现，来自共生海洋藻类共生藻属（Symbiodinium sp.）的虫黄藻毒素 - B在浓度为10^(-7)-10^(-5) M时可引起兔离体主动脉的浓度依赖性收缩。维拉帕米（10^(-6) M）和甲芬那酸（10^(-5) M）在较低浓度（10^(-7)-10^(-6) M）时可显著减弱对虫黄藻毒素 - B的收缩反应，但在较高浓度（3×10^(-6)-10^(-5) M）时则不然。酚妥拉明（10^(-6) M）可部分抑制对虫黄藻毒素 - B的反应，而哇巴因（10^(-5) M）则使其增强。然而，河豚毒素（10^(-6) M）、甲基麦角新碱（10^(-6) M）、氯苯那敏（10^(-6) M）或吲哚美辛（3×10^(-6) M）对其无影响。在无钙溶液中孵育可消除虫黄藻毒素 - B诱导的收缩。收缩反应随Ca2+（0.03和10 mM）或Sr2 +（0.10和10 mM）以浓度依赖性方式增加。用维拉帕米（10^(-6)或5×10^(-6) M）处理后，在存在虫黄藻毒素 - B的情况下，Ca2+和Sr2+的浓度 - 收缩反应曲线平行右移。MgCl2（10 mM）比维拉帕米更明显地使Ca2+的浓度 - 反应曲线右移。虫黄藻毒素 - B增加了主动脉组织中的Na+含量并降低了组织中的K+含量，表明虫黄藻毒素 - B增加了跨质膜的Na+和K+通透性。这些结果表明，虫黄藻毒素 - B诱导的主动脉收缩主要是由对平滑肌的直接作用引起的，即Ca2+通透性增加，这至少部分是通过电压敏感性Ca2+通道以及平滑肌细胞膜中的非选择性阳离子通道发生的。
