Effect of KT-362, a putative intracellular calcium antagonist, on norepinephrine-induced contractions and inositol monophosphate accumulation in canine femoral artery.
Effect of KT-362, a putative intracellular calcium antagonist, on norepinephrine-induced contractions and inositol monophosphate accumulation in canine femoral artery.
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KT-362（一种假定的细胞内钙拮抗剂）对去甲肾上腺素诱导的犬股动脉收缩和肌醇单磷酸积累的影响。
DOI：
10.1097/00005344-198903000-00020
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发表时间：
1989
影响因子：
3
通讯作者：
Gross,GJ
中科院分区：
文献类型：
--
作者：
Eskinder,H;Hillard,CJ;Wilke,RA;Gross,GJ
本研究的目的是确定细胞内钙拮抗剂KT-362是否抑制去甲肾上腺素-IN Hi诱导的收缩和[3 H]肌醇预孵育犬股动脉中肌醇一磷酸（IP）的积累。去甲肾上腺素剂量依赖性地增加收缩张力，并产生了平行刺激肌醇磷脂水解IP积累。这种刺激被选择性[α] 1肾上腺素受体拮抗剂抑制。哌唑嗪（0.1 [mu] M），表明NE诱导的肌醇磷脂水解刺激与犬股动脉中的[α] 1肾上腺素受体活化偶联。用硝酸甘油（100 [mu] M）预处理。8-环磷酸鸟苷（cGMP）（1 [mu] M）或地尔硫卓（40 [mu] M）抑制NE产生的收缩反应，然而，这些药物对NE诱导的IP积累没有显着影响。与此相反，KT-362（10-100 [mu] M）预处理大大抑制NE诱导的收缩和IP积累。KT-362在正常和零钙缓冲液中也能显著抑制NE诱导的收缩，而地尔硫卓（40 [mu] M）在零钙缓冲液中没有作用。这些结果表明，KT-362的作用机制不同于地尔硫卓、硝酸甘油和8-Br cGMP。这些数据表明，KT-362拮抗NE诱导的血管收缩反应的机制之一是通过减少犬股动脉中肌醇磷脂的水解。
The purpose of the present study was to determine if the intracellular calcium antagonist, KT-362, inhibits norepinephrine-IN Hi induced contractions and inositol monophosphate (IP) accumulation in canine femoral arteries preincubated with [3H] inositol. Norepinephrine dose-dependently increased contractile tension and produced a parallel stimulation of inositol phospholipid hydrolysis as measured by IP accumulation. This stimulation was inhibited by the selective [alpha] 1 adrenoceptor antagonist. prazosin (0.1 [mu] M), indicating that the NE-induced stimulation of inositol phospholipid hydrolysis is coupled to [alpha] 1 adrenoceptor activation in canine femoral artery. Pretreatment with nitroglycerin (100 [mu] M). 8-Brcyclic guanosine monophosphate (cGMP)(1 [mu] M), or diltiazem (40 [mu] M) inhibited contractile responses produced by NE; however, these agents had no significant effect on NE-indueed IP accumulation. In contrast, pretreatment with KT-362 (10-100 [mu] M) greatly inhibited both the NE-induced contractions and IP accumulation. KT-362 also produced a marked inhibition of NE-induced contractions in normal as well as zero calcium buffer, whereas diltiazem (40 [mu] M) had no effect in zero calcium buffer. These results indicate that the mechanism of action of KT-362 differs from diltiazem, nitroglycerin, and 8-Br cGMP. and these data suggest that one of the mechanisms by which KT-362 antagonizes NE-induced vasoconstrictor responses is by decreasing inositol phospholipid hydrolysis in canine femoral artery.