Hashizume H, Akiyama K, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Eur J Pharmacol. 1994 Dec 12;271(1):1-8. doi: 10.1016/0014-2999(94)90257-7.
The effects of different groups of substances (beta-adrenoceptor antagonists, Ca2+ channel blockers and vasodilators) which are known to have antiischemic properties were studied on veratridine-induced hypercontracture. Veratridine increases Na+ influx by slowing the inactivation process of the Na+ channel, thereby inducing a continuously increased Na+ entry in depolarized cells. Veratridine (6.3 x 10(-6) M) produced a change in cell shape from rod-shape to round, resulting from hypercontracture of cells. Before treatment with veratridine the proportion of rod-shaped cells was 70% and fell to 0% 5 min after the treatment with veratridine. dl-Propranolol, d-propranolol, l-penbutolol, d-penbutolol, nisoldipine, and dilazep all inhibited veratridine-induced hypercontracture dose dependently. In contrast, acebutolol, atenolol, timolol, nifedipine, diltiazem, and nitroglycerin did not inhibit the rounding of cells. Concomitantly with the rounding of cells, the [Ca2+]i was increased by veratridine. dl-Propranolol, d-propranolol and dilazep prevented the increase of [Ca2+]i induced by veratridine, whereas timolol and nitroglycerin did not. These results show that dl-propranolol, d-propranolol, l-penbutolol, d-penbutolol, nisoldipine, and dilazep possess Na+ channel blocking actions on the veratridine-modified Na+ channel, thereby preventing excessive Na+ influx and secondary Ca2+ overload.
已知具有抗缺血特性的不同组物质（β - 肾上腺素受体拮抗剂、Ca2+通道阻滞剂和血管扩张剂）对藜芦碱诱导的超收缩作用进行了研究。藜芦碱通过减缓Na+通道的失活过程增加Na+内流，从而在去极化细胞中诱导Na+持续进入增加。藜芦碱（6.3×10(-6) M）使细胞形状从杆状变为圆形，这是细胞超收缩的结果。在用藜芦碱处理前，杆状细胞的比例为70%，在用藜芦碱处理5分钟后降至0%。dl - 普萘洛尔、d - 普萘洛尔、l - 喷布洛尔、d - 喷布洛尔、尼索地平及地拉卓均剂量依赖性地抑制藜芦碱诱导的超收缩。相反，醋丁洛尔、阿替洛尔、噻吗洛尔、硝苯地平、地尔硫䓬及硝酸甘油未抑制细胞变圆。伴随细胞变圆，藜芦碱使[Ca2+]i升高。dl - 普萘洛尔、d - 普萘洛尔及地拉卓可防止藜芦碱诱导的[Ca2+]i升高，而噻吗洛尔及硝酸甘油则不能。这些结果表明，dl - 普萘洛尔、d - 普萘洛尔、l - 喷布洛尔、d - 喷布洛尔、尼索地平及地拉卓对藜芦碱修饰的Na+通道具有Na+通道阻断作用，从而防止过量的Na+内流及继发性Ca2+超载。
