Azelastine effects on electrical and mechanical activities of guinea pig papillary muscles.
Azelastine effects on electrical and mechanical activities of guinea pig papillary muscles.
复制标题
氮卓斯汀对豚鼠乳头肌电和机械活动的影响。
DOI：
10.1016/0014-2999(89)90263-x
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发表时间：
1989
影响因子：
5
通讯作者：
Sperelakis,N
中科院分区：
文献类型：
--
作者：
Molyvdas,PA;James,FW;Sperelakis,N
采用常规微电极技术，在豚鼠乳头肌（37°C下用含氧台氏液灌流）中研究了临床研究中的新型抗哮喘药物氮卓斯汀对正常快动作电位（AP）和慢AP的影响。在25 mM [K] 0存在的情况下，10− 7 M异丙肾上腺素、10− 5 M组胺、db-cAMP（3 mM）或10 mM TEA诱导慢AP，使快Na+通道电压失活。在10 - 5 M时，氮卓斯汀降低了慢AP的最大上升速率（+V ~ max）和收缩力。在3 × 10 - 5 M时，氮卓斯汀进一步降低+V最大值和慢AP的振幅;在10 - 4 M时，慢AP和收缩完全消失。药物洗脱后，出现自动性。在存在10− 4 M氮卓斯汀的情况下，将[Ca] 0浓度从1.8增加到3.6和5.4 mM导致缓慢AP和收缩的部分恢复。氮卓斯汀也可抑制快速AP。在10 - 5和3 × 10 - 5 M时，氮卓斯汀可缩短快AP的+V max和50%复极化时的AP时程（APD）。10− 4 M氮卓斯汀30分钟后观察到快速AP完全阻滞和收缩抑制。洗脱3-5 h后，兴奋性恢复，+V max降低，APD_（90）延长。结论：氮卓斯汀对慢钙通道和快钠通道均有抑制作用。缓慢的恢复表明药物可能在细胞内积聚，并对收缩产生长期抑制作用。
The effects of azelastine, a new anti-asthmatic drug under clinical investigation, were studied on both normal fast action potentials (APs) and slow APs using conventional microelectrode techniques in guinea pig papillary muscles (superfused with oxygenated Tyrode solution at 37°C). Slow APs were induced by either 10−7M isoproterenol, 10−5M histamine, db-cAMP (3 mM) or 10 mM TEA, in the presence of 25 mM [K]0to voltage inactive the fast Na+channels. At 10−5M, azelastine depressed the maximum rate of rise (+V̇max) of the slow APs and the force of contraction. At 3 × 10−5M, azelastine further reduced +V̇maxand the amplitude of the slow APs; complete abolishion of slow APs and contractions occurred at 10−4M. Upon washout of the drug, automaticity appeared. In the presence of 10−4M azelastine, increasing the [Ca]0concentration from 1.8 to 3.6 and 5.4 mM caused partial recovery of the slow APs and contractions. The fast APs were also depressed by azelastine. At 10−5and 3 × 10−5M, azelastine reduced +V̇maxand the AP duration at 50% repolarization (APD)50) of the fast APs. Complete block of the fast APs and suppression of contractions were observed after 30 min at 10−4M azelastine. After 3–5 h of washout, excitability recovered; however, +V̇maxwas depressed and APD90was prolonged. It is concluded that azelastine inhibits the slow Ca2+channels and the fast Na+channels. The slow recovery suggests that the drug may accumulate inside the cells, and exert a prolonged inhibitory effect on contraction.