Low [Mg(2+)](o) induces contraction and [Ca(2+)](i) rises in cerebral arteries: roles of ca(2+), PKC, and PI3.
Low [Mg(2+)](o) induces contraction and [Ca(2+)](i) rises in cerebral arteries: roles of ca(2+), PKC, and PI3.
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DOI：
10.1152/ajpheart.2000.279.6.h2898
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发表时间：
2000-12
期刊：
影响因子：
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通讯作者：
Z. Yang;J. Wang;T. Zheng;B. T. Altura;B. M. Altura
中科院分区：
文献类型：
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作者：
Z. Yang;J. Wang;T. Zheng;B. T. Altura;B. M. Altura
去除细胞外Ca（2+）浓度（[Ca（2+）]（o））和用电压门控Ca（2+）通道拮抗剂预处理犬基底动脉环（维拉帕米），肌浆网Ca（2+）泵的选择性拮抗剂[毒胡萝卜素（TSG）]，咖啡因加ryanodine敏感性Ca（2+）释放的特异性拮抗剂（ryanodine）或D-肌肌醇1，4，5-三磷酸[Ins（1，4，5）P（3）]介导的Ca（2+）释放拮抗剂（肝素）显著减弱低细胞外Mg（2+）浓度（[Mg（2+）]（o））诱导的收缩。用Gö-6976 [蛋白激酶C-α（PKC-α）和PKC-β I选择性拮抗剂]、双吲哚马来酰亚胺I（Bis，PKC特异性拮抗剂）和渥曼青霉素或LY-294002 [磷脂酰肌醇-3激酶（PI 3 Ks）选择性拮抗剂]预处理血管可显著抑制低[Mg（2+）]（o）诱导的收缩。这些拮抗剂也被发现以浓度依赖性方式舒张低[Mg（2+）]（o）引起的动脉收缩。缺乏[Ca（2+）]（o）和用维拉帕米、TSG、肝素或咖啡因加ryanodine预孵育细胞可显著减弱由低[Mg（2+）]（o）培养基诱导的胞内Ca（2+）浓度（[Ca（2+）]（i））的瞬时和持续升高。低[Mg（2+）]（o）引起的[Ca（2+）]（i）增加在Gö-6976、Bis、渥曼青霉素或LY-294002存在下也被显著抑制。本研究表明，电压门控性Ca（2+）通道的Ca（2+）内流和细胞内钙库的Ca（2+）释放[Ins（1，4，5）P（3）敏感和ryanodine敏感]在低[Mg（2+）]（o）介质引起的离体犬基底动脉收缩中起重要作用。这种收缩明显与PKC亚型和PI 3 Ks的激活相关。
Removal of extracellular Ca(2+) concentration ([Ca(2+)](o)) and pretreatment of canine basilar arterial rings with either an antagonist of voltage-gated Ca(2+) channels (verapamil), a selective antagonist of the sarcoplasmic reticulum Ca(2+) pump [thapsigargin (TSG)], caffeine plus a specific antagonist of ryanodine-sensitive Ca(2+) release (ryanodine), or a D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)]- mediated Ca(2+) release antagonist (heparin) markedly attenuates low extracellular Mg(2+) concentration ([Mg(2+)](o))-induced contractions. Low [Mg(2+)](o)-induced contractions are significantly inhibited by pretreatment of the vessels with Gö-6976 [a protein kinase C-alpha (PKC-alpha)- and PKC-betaI-selective antagonist], bisindolylmaleimide I (Bis, a specific antagonist of PKC), and wortmannin or LY-294002 [selective antagonists of phosphatidylinositol-3 kinases (PI3Ks)]. These antagonists were also found to relax arterial contractions induced by low [Mg(2+)](o) in a concentration-dependent manner. The absence of [Ca(2+)](o) and preincubation of the cells with verapamil, TSG, heparin, or caffeine plus ryanodine markedly attenuates the transient and sustained elevations in the intracellular Ca(2+) concentration ([Ca(2+)](i)) induced by low-[Mg(2+)](o) medium. Low [Mg(2+)](o)-produced increases in [Ca(2+)](i) are also suppressed markedly in the presence of Gö-6976, Bis, wortmannin, or LY-294002. The present study suggests that both Ca(2+) influx through voltage-gated Ca(2+) channels and Ca(2+) release from intracellular stores [both Ins(1,4,5)P(3) sensitive and ryanodine sensitive] play important roles in low-[Mg(2+)](o) medium-induced contractions of isolated canine basilar arteries. Such contractions are clearly associated with activation of PKC isoforms and PI3Ks.