Pushkarev V M, Tron'ko N D
Probl Endokrinol (Mosk). 1992 Sep-Oct;38(5):45-9.
The effects of chlorpromazine, a calmodulin inhibitor, on K(+)-dependent regulation of aldosterone biosynthesis were studied in sections and dispersed adrenocortical cells of guinea pigs. K ions in concentrations 5-11 mM significantly (p < 0.01) stimulated aldosterone and protein biosynthesis and protein phosphorylation in sections and cells of the guinea pig adrenal cortex. Using the radioautography of P-labeled polypeptides separated in polyacrylamide gel, the authors have demonstrated K+ enhancement of phosphate incorporation in the proteins with molecular masses of 40 and 75 kD in the cytosols and of 75 kD proteins in the mitochondria. Chlorpromazine in concentration 50 microM reduced K(+)-stimulated steroidogenesis and protein phosphorylation, simultaneously increasing labeled phosphate incorporation in the proteins in low K+ concentrations, not stimulating steroidogenesis. K(+)-stimulated protein biosynthesis was virtually unchanged in the presence of chlorpromazine. Increased K+ concentration in the medium resulted in reduction of cGMP concentration in adrenal cortex sections. The nucleotide level grew in the presence of chlorpromazine in elevated concentrations of K+ and reduced if the ion concentrations were low (1-3 mM). The mechanisms of chlorpromazine effect on K(+)-dependent steroidogenesis changes, protein phosphorylation and cGMP levels in the adrenocortical tissue are discussed, as is the role of calmodulin in K(+)-dependent regulation of aldosterone biosynthesis.
在豚鼠的肾上腺皮质切片和分散的肾上腺皮质细胞中，研究了钙调蛋白抑制剂氯丙嗪对醛固酮生物合成的钾离子依赖性调节作用。浓度为5 - 11 mM的钾离子显著（p < 0.01）刺激豚鼠肾上腺皮质切片和细胞中的醛固酮和蛋白质生物合成以及蛋白质磷酸化。通过对聚丙烯酰胺凝胶中分离的P标记多肽进行放射自显影，作者证明钾离子增强了细胞质中分子量为40和75 kD的蛋白质以及线粒体中75 kD蛋白质的磷酸掺入。浓度为50 μM的氯丙嗪降低了钾离子刺激的类固醇生成和蛋白质磷酸化，同时在低钾离子浓度下增加了蛋白质中标记磷酸的掺入，而低钾离子浓度不刺激类固醇生成。在氯丙嗪存在的情况下，钾离子刺激的蛋白质生物合成实际上没有变化。培养基中钾离子浓度升高导致肾上腺皮质切片中cGMP浓度降低。在高钾离子浓度下，氯丙嗪存在时核苷酸水平升高，而在低钾离子浓度（1 - 3 mM）时降低。讨论了氯丙嗪对肾上腺皮质组织中钾离子依赖性类固醇生成变化、蛋白质磷酸化和cGMP水平的影响机制，以及钙调蛋白在醛固酮生物合成的钾离子依赖性调节中的作用。
