Podesta E J, Milani A, Steffen H, Neher R
Biochem J. 1980 Feb 15;186(2):391-7. doi: 10.1042/bj1860391.
The corticotropin-induced increase of total intracellular and receptor-bound cyclic AMP in isolated rat adrenocortical cells was strictly dependent on extracellular Ca(2+). A rise in bound cyclic AMP with rising Ca(2+) concentrations was accompanied by a decrease in free cyclic AMP-receptor sites. A Ca(2+)-transport inhibitor abolished the rise in bound cyclic AMP induced by corticotropin. These data suggested that during stimulation by corticotropin some Ca(2+) has to be taken up in order to promote the rise of the relevant cyclic AMP pool. In agreement with this view, adenylate cyclase activity from isolated cells proved also to be dependent on a sub-millimolar Ca(2+) concentration in the presence of corticotropin and GTP. When cells were treated under specific conditions, corticosterone production could be activated by Ca(2+) in the absence of corticotropin (cells primed for Ca(2+)). Ca(2+)-induced steroidogenesis of these cells, in the absence of corticotropin, was also accompanied by an increase in total intracellular and receptor-bound cyclic AMP, as was found previously with corticotropin-induced steroidogenesis in non-primed cells. Calcium ionophores increasing the cell uptake of Ca(2+) were not able, however, to increase the cyclic AMP pools in non-primed cells, unlike corticotropin in nonprimed cells or Ca(2+) in cells primed for Ca(2+). It was concluded that during stimulation by either corticotropin or Ca(2+) a possible cellular uptake of Ca(2+) must be very limited and directed to a specific site which may affect the coupling of the hormone-receptor-adenylate cyclase complex.
促肾上腺皮质激素诱导的大鼠肾上腺皮质分离细胞内总环磷酸腺苷（cAMP）及与受体结合的cAMP增加严格依赖于细胞外钙离子（Ca(2+)）。随着Ca(2+)浓度升高，结合的cAMP增加，同时游离的cAMP受体位点减少。一种Ca(2+)转运抑制剂消除了促肾上腺皮质激素诱导的结合cAMP升高。这些数据表明，在促肾上腺皮质激素刺激过程中，必须摄取一些Ca(2+)以促进相关cAMP池的升高。与此观点一致，在存在促肾上腺皮质激素和鸟苷三磷酸（GTP）的情况下，分离细胞的腺苷酸环化酶活性也依赖于亚毫摩尔浓度的Ca(2+)。当细胞在特定条件下处理时，在无促肾上腺皮质激素的情况下（细胞对Ca(2+)致敏），Ca(2+)可激活皮质酮生成。这些细胞在无促肾上腺皮质激素时Ca(2+)诱导的类固醇生成也伴随着细胞内总cAMP及与受体结合的cAMP增加，这与之前在未致敏细胞中促肾上腺皮质激素诱导的类固醇生成情况相同。然而，与未致敏细胞中的促肾上腺皮质激素或对Ca(2+)致敏的细胞中的Ca(2+)不同，增加细胞对Ca(2+)摄取的钙离子载体不能增加未致敏细胞中的cAMP池。得出的结论是，在促肾上腺皮质激素或Ca(2+)刺激过程中，Ca(2+)可能的细胞摄取必须非常有限且指向一个可能影响激素-受体-腺苷酸环化酶复合物偶联的特定位点。
