Calcium entry via L-type calcium channels acts as a negative regulator of adenylyl cyclase activity and cyclic AMP levels in cardiac myocytes.
Calcium entry via L-type calcium channels acts as a negative regulator of adenylyl cyclase activity and cyclic AMP levels in cardiac myocytes.
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发表时间：
1993-10
影响因子：
3.6
通讯作者：
H. J. Yu;H. Ma;R. D. Green
中科院分区：
文献类型：
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作者：
H. J. Yu;H. Ma;R. D. Green
已经确定，β-肾上腺素能激动剂的变力作用是通过腺苷酸环化酶活性的刺激和随后cAMP依赖性蛋白激酶对特定蛋白的磷酸化介导的。L型钙通道被认为是磷酸化的蛋白质之一;钙通道的磷酸化被认为增加钙进入肌细胞，这至少部分地负责正性肌力作用。目前的研究表明，随着细胞外钙的降低，异丙肾上腺素的cAMP升高作用增加，并且在细胞外钙存在的情况下，钙通道阻滞剂增强异丙肾上腺素的cAMP升高作用。这种作用不依赖于对cAMP catalysts的作用，也不特异于β-肾上腺素能受体，因为毛喉素的cAMP升高作用受到类似的影响。心脏膜腺苷酸环化酶活性的测量表明，亚微摩尔浓度的Ca 2+直接抑制腺苷酸环化酶活性。这些结果表明，响应于β-肾上腺素能受体刺激，通过L-型钙通道增加的Ca 2+进入充当β受体刺激对腺苷酸环化酶活性的影响的负调节剂。
It is well established that the inotropic effect of beta-adrenergic agonists is mediated by the stimulation of adenylyl cyclase activity and the subsequent phosphorylation of specific proteins by cAMP-dependent protein kinase. The L-type calcium channel is believed to be one of the proteins phosphorylated; the phosphorylation of calcium channels is believed to increase calcium entry into myocytes, which is, at least in part, responsible for the positive inotropic effect. The present studies show that the cAMP-elevating effect of isoproterenol is increased as extracellular calcium is lowered and that calcium channel blockers potentiate the cAMP-elevating effect of isoproterenol in the presence in extracellular calcium. This effect is not dependent on effects on cAMP catabolism and is not specific for beta-adrenergic receptors, because the cAMP-elevating effect of forskolin is similarly affected. Measurements of adenylyl cyclase activity in cardiac membranes show that submicromolar Ca2+ concentrations directly inhibit adenylyl cyclase activity. These results demonstrate that increased entry of Ca2+ via L-type calcium channels in response to beta-adrenergic receptor stimulation acts as a negative regulator of the effect of beta receptor stimulation on adenylyl cyclase activity.