摘要
用离体兔主动脉和豚鼠心房研究山茛菪碱(654-2)负性变力和变频作用及其机理,654-2能拮抗CaC1_2和异丙肾上腺素的正性变力和变频作用,呈非竞争性拮抗。对去甲肾上腺素两种收缩成分均有抑制作用,对豚鼠心房频率依赖性收缩亦有抑制,表明654-2的负性变力和变频作用与其钙拮抗作用有关,对细胞外钙经两种钙通道的跨膜内流和内钙释放均有不同程度的抑制。
In spontaneously beating right atria of guinea pig, anisodamine (654-2) could antagonize Ca^(2+)-induced positive chronotropic response. Similar to verapamil (Ver), 654-2 shifte isoprenaline (Iso) dose-response (beat rate) curve non-parallelly to the right with decrease of its maximum effect, showing non-competitive antagonism. 654-2 and Ver produced frequency-dependent depression of contractile force of guinea pig left atria but Ver could inverse the frequency-contractile curve from positive staircase into negative one. Both 654-2 and Ver had inhibitory effects on post-rest potentiation. In isolated rabbit aorta, 654-2 had antagonist effect against two contractile compoments induced by norepinephrine. The data showed that 654-2 shifted Ca^(2+) dose-response (contraction) curve non-parallelly to the right with decrease its maximum effect in high K^+ (40mM) solution, showing non-competitive antagonism. This study indicates that 654-2 exerted negative inotropic and chronotropic effects in isolated vessels and atria because 654-2 might inhibit two calcium channels (PDC and ROC) and release of intracellular calcium. These results suggest that 654-2 possesses non-specific calcium-antagonism.
关键词
山莨菪碱
主动脉
钙拮抗剂
anisodamine
aorta
calcium channel blockers
ion channels
rabbits
guinea pigs
