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首页> 外文期刊>Life sciences >Inhibition of cyclic AMP accumulation by endothelin is pertussis toxin sensitive and calcium independent in isolated adult feline cardiac myocytes.
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Inhibition of cyclic AMP accumulation by endothelin is pertussis toxin sensitive and calcium independent in isolated adult feline cardiac myocytes.

机译：内皮素对环状AMP的抑制作用是对百日咳毒素敏感的，并且在离体成年猫心脏心肌细胞中钙的依赖性不强。

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摘要

The aims of this study were to determine whether endothelin-1 (ET-1), a positive inotropic agent, altered the production of cyclic AMP (cAMP) in adult feline cardiac myocytes and to characterize the effect with respect to G-protein-coupling and calcium regulation of adenylyl cyclase. ET-1 inhibited basal and/or stimulated cAMP accumulation in the intact cardiac myocyte and in membrane preparations in a dose-dependent manner. In intact cells, maximal inhibition of forskolin-stimulated cAMP accumulation was 90-95% with an EC50 of 5 x 10(-10) M. Inhibition of isoproterenol-stimulated cAMP was biphasic with maximal inhibition of 70% observed by 10(-11)M; at higher doses inhibition was not consistently observed. The inhibitory response to ET-1 occurred in the absence or presence of isobutylmethylxanthine suggesting that activation of cAMP phosphodiesterases was not the means for reducing cAMP levels. Prior exposure of cardiac myocytes to 100ng/ml pertussis toxin blocked the inhibitory action of ET-1, indicating that this response is mediated through the involvement of a pertussis toxin-sensitive G-protein such as Gi. Studies carried out in the absence of extracellular calcium and under conditions of cell-loading with the intracellular calcium chelator, 1,2-bis-(2-aminophenoxy)-ethane-N,N,N'N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM), suggest that the mechanism by which ET-1 inhibits cAMP accumulation is not calcium-dependent. Thus, inhibition of cAMP accumulation by ET-1 appears to be mediated through a pertussis toxin sensitive protein rather than by activation of phosphodiesterases or calcium inhibition of cardiac forms of adenylyl cyclase. Though unlikely to play a role in the positive inotropic effect of ET-1, transduction of ET-1 responses through Gi suggests another means for regulation of growth in these adult cardiac myocytes.
机译：这项研究的目的是确定正性肌力药物内皮素-1（ET-1）是否改变了成年猫心肌细胞中环AMP（cAMP）的产生，并表征了对G蛋白偶联的影响和腺苷酸环化酶的钙调节。 ET-1以剂量依赖的方式抑制了完整心肌细胞和膜制剂中基础和/或刺激的cAMP积累。在完整细胞中，福司柯林刺激的cAMP积累的最大抑制为90-95％，EC50为5 x 10（-10）M.异丙肾上腺素刺激的cAMP的抑制是双相的，10（-11）观察到的最大抑制为70％。 ）M;在较高剂量下未始终观察到抑制作用。对ET-1的抑制反应发生在不存在或存在异丁基甲基黄嘌呤的情况下，这表明激活cAMP磷酸二酯酶不是降低cAMP水平的手段。心肌细胞先前暴露于100ng / ml百日咳毒素可阻断ET-1的抑制作用，表明该反应是通过百日咳毒素敏感的G蛋白（如Gi）的参与介导的。在不存在细胞外钙的情况下和在细胞内钙螯合剂负载细胞的条件下进行的研究，是1,2-双-（2-氨基苯氧基）-乙烷-N，N，N'N'-四乙酸-乙酰氧基甲基酯（BAPTA / AM），表明ET-1抑制cAMP积累的机制不是钙依赖性的。因此，ET-1对cAMP积累的抑制作用似乎是通过百日咳毒素敏感蛋白而不是磷酸二酯酶的激活或钙对心脏形式的腺苷酸环化酶的抑制来介导的。尽管不太可能在ET-1的正性肌力作用中发挥作用，但通过Gi转导ET-1反应提示了另一种调节这些成年心肌细胞生长的方法。

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