Activation of a β-adrenergic-sensitive signal transduction pathway by the secosteroid hormone 1,25-(OH)2-vitamin D3 in chick heart
Activation of a β-adrenergic-sensitive signal transduction pathway by the secosteroid hormone 1,25-(OH)2-vitamin D3 in chick heart
复制标题
DOI：
10.1006/jmcc.1999.0942
复制
发表时间：
1999-05-01
影响因子：
5
通讯作者：
Boland, RL
中科院分区：
文献类型：
--
作者：
Santillán, GE;Vazquez, G;Boland, RL
在最近的研究中，我们已经确定1 α，25-二羟基维生素D-3 [1，25（OH）（2）D-3]通过非基因组作用快速刺激鸡心肌中二氢吡啶敏感性钙通道介导的Ca 2+内流，该作用伴随着45 kDa微粒体膜蛋白的PKA依赖性磷酸化。为了探讨1，25（OH）（2）D-3在心脏中激活的信号传导途径，我们采用培养的鸡胚心脏细胞（肌细胞）和分化的成人心肌薄片标本，比较了开环类固醇激素和β肾上腺素能激动剂异丙肾上腺素（IPT）的作用。IPT可再现1，25（OH）（2）D-3引起的Ca-45（2+）摄取和细胞内钙（[Ca ~（2+）]（i））增加、cAMP蓄积和微粒体蛋白磷酸化的变化。当使用甾醇和β-肾上腺素能激动剂进行联合治疗时，未观察到这些参数的叠加刺激，表明共同的信号转导途径介导1，25（OH）（2）D-3和IPT的作用。研究了鸟嘌呤核苷酸结合蛋白（G蛋白）在1，25（OH）（2）D-3诱导的心脏变化中的参与。AlF 4-，一种G蛋白的激活剂，以及霍乱和百日咳毒素，如1，25（OH）（2）D-3，增加了心肌细胞对Ca-45（2+）的摄取，AlF 4-没有进一步刺激1，25（OH）（2）D-3的作用，从而表明G蛋白参与了激素作用。此外，1，25（OH）（2）D-3增强百日咳毒素，但不能改变胆汁毒素依赖的心肌细胞Ca 2+内流。总之，这些结果提供的证据表明，1，25（OH）（2）D-3对心肌钙内流的非基因组作用：涉及与Gs蛋白偶联的β-肾上腺素能敏感性腺苷酸环化酶/cAMP/PKA途径的调节。(C)北京：科学出版社.
In recent studies we have established that 1 alpha,25-dihydroxy-vitamin D-3 [1, 25(OH)(2)D-3] rapidly stimulates dihydropyridine-sensitive calcium channel-mediated Ca2+ influx in chick cardiac muscle by a non-genomic action which is accompanied by PKA-dependent phosphorylation of a 45 kDa microsomal membrane protein. To investigate the signal transduction pathway activated by 1,25(OH)(2)D-3 in heart, we have compared the effects of the secosteroid hormone with those of the beta-adrenergic agonist isoproterenol (IPT) by employing cultured chick embryonic cardiac cells (myocytes) and thin-slice preparations of differentiated adult heart muscle. The increases in Ca-45(2+) uptake and intracellular calcium ([Ca2+](i)), cyclic AMP accumulation and changes in microsomal protein phosphorylation evoked by 1,25(OH)(2)D-3 could be reproduced by IPT. When combined treatments with the sterol and the beta-adrenergic agonist were performed, no additive stimulation of these parameters was observed, suggesting that a common signal transduction pathway mediates the effects of 1,25(OH)(2)D-3 and IPT, The participation of a guanine nucleotide binding protein (G protein) in the 1,25(OH)(2)D-3-induced changes in heart was investigated. AlF4-, an activator of G proteins, and cholera and pertussis toxins, like 1,25(OH)(2)D-3 increased Ca-45(2+) uptake by myocytes, AlF4- did not further stimulate the effects of 1,25(OH)(2)D-3 thereby showing that a G protein is involved in the hormone action. Moreover, 1,25(OH)(2)D-3 potentiated pertussis toxin but was unable to modify choleric toxin-dependent myocyte Ca2+ influx. Altogether, these results provide evidence indicating that the non-genomic action of 1,25(OH)(2)D-3 on cardiac muscle calcium influx: involves modulation of the beta-adrenergic-sensitive adenylyl cyclase/cAMP/PKA pathway coupled to a Gs protein. (C) 1999 Academic Press.