Effects of stilbenedisulfonic acid derivatives on the cAMP-regulated chloride current in cardiac myocytes.
Effects of stilbenedisulfonic acid derivatives on the cAMP-regulated chloride current in cardiac myocytes.
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二苯乙烯二磺酸衍生物对心肌细胞中 cAMP 调节的氯电流的影响。
DOI：
10.1007/bf00375068
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Harvey,RD
中科院分区：
文献类型：
--
作者：
Harvey,RD
二苯乙烯二磺酸衍生物在许多不同的制备中已被证明可以直接阻断Cl−通道。因此，使用膜片钳技术在室温下记录全细胞Cl−电流，检查这些化合物作为研究豚鼠心室肌细胞cAMP依赖性Cl−电流（Icl）的工具的效用。结果发现，4-乙酰氨基-4 ′-异硫氰基二苯乙烯-2，2 ′-二磺酸（SITS）增加，而不是减少，异丙肾上腺素（ISO）激活的Cl−电流。然而，SITS单独刺激很少或没有持续电流，表明SITS通过与ISO的协同效应激活Cl−电流。4，4 ′-Diisothiocyanostilbene-2，2 ′-disulfonic acid（DIDS）也增强了ISO激活的Cl−电流。而4，4 ′-二硝基二苯乙烯-2，2 ′-二磺酸（DNDS）则无此作用。SITS还表现出对相同细胞中ISO增强的Ca 2+电流的协同作用，表明它影响了Cl−和Ca 2+通道的β-肾上腺素能调节途径。SITS对用毛喉素直接激活腺苷酸环化酶或暴露于膜渗透性cAMP衍生物8-溴腺苷3′，5 ′-环一磷酸刺激的Cl−电流没有影响。这表明SITS和DIDS可能通过对β-肾上腺素能受体的作用增强ISO激活的Cl−电流。结论是，这些芪二磺酸衍生物不是有效的cAMP激活的Cl−通道在心室肌细胞的拮抗剂。
Stilbenedisulfonic acid derivatives have been shown to block Cl−channels directly in many different preparations. Therefore, the utility of these compounds as tools for studying the cAMP-dependent Cl−current (Icl) in guinea-pig ventricular myocytes was examined using the patch-clamp technique to record whole-cell Cl−currents at room temperature. It was found that 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS) increased, rather than decreased, the isoproterenol (ISO)-activated Cl−current. However, SITS alone stimulated little or no sustained current, suggesting that SITS activates the Cl−current through a synergistic effect with ISO. 4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) also enhanced the ISO-activated Cl−current. However, 4,4′-dinitrostilbene-2,2′-disulfonic acid (DNDS) did not have any effect. SITS also exhibited a synergistic effect on the ISO-enhanced Ca2+current in the same cells, suggesting that it affects the pathway involved inβ-adrenergic regulation of both Cl−and Ca2+channels. SITS had no effect on the Cl−current stimulated by direct activation of adenylate cyclase with forskolin or exposure to the membrane-permeable cAMP derivative 8-bromoadenosine 3′,5′-cyclic monophosphate. This suggests that SITS and DIDS may enhance the ISO-activated Cl−current via an effect on theβ-adrenergic receptor. It is concluded that these stilbenedisulfonic acid derivatives are not effective antagonists of cAMP-activated Cl−channels in cardiac ventricular myocytes.