Caldwell K K, Boyajian C L, Cooper D M
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
Cell Calcium. 1992 Feb;13(2):107-21. doi: 10.1016/0143-4160(92)90004-c.
The regulation of adenylyl cyclase activity by varying concentrations of Ca2+ was examined in plasma membrane preparations derived from a number of neural and non-neural cells. Enzyme activity in neural tissue (i.e. cerebellum) neural-derived pheochromocytoma PC12 cells and certain endocrine cells (i.e. pancreatic RINm5f and parathyroid cells) was stimulated by physiologic concentrations of Ca2+ by a calmodulin (CaM)-dependent mechanism. In contrast, adenylyl cyclase activity in non-neural cells (e.g. platelets and GH3 cells) was not stimulated by Ca2+. In these latter sources, enzyme activity was inhibited by increasing concentrations of Ca2+, independent of CaM. In liver membranes, Ca2+ and/or CaM did not alter adenylyl cyclase activity. These results demonstrate that the effects exerted by physiologic concentrations of Ca2+ on adenylyl cyclase activity range from CaM-dependent stimulation of activity to no effect, to CaM-independent inhibition of activity. The actions of Ca2+ on adenylyl cyclase may be major contributors to the various synergistic or antagonistic interactions that are seen between cAMP-generating and Ca(2+)-mobilizing systems.
在来源于多种神经和非神经细胞的质膜制剂中，研究了不同浓度的Ca2+对腺苷酸环化酶活性的调节作用。神经组织（即小脑）、神经来源的嗜铬细胞瘤PC12细胞和某些内分泌细胞（即胰腺RINm5f细胞和甲状旁腺细胞）中的酶活性，通过钙调蛋白（CaM）依赖性机制受到生理浓度Ca2+的刺激。相比之下，非神经细胞（如血小板和GH3细胞）中的腺苷酸环化酶活性不受Ca2+刺激。在这些后者来源中，酶活性随着Ca2+浓度增加而受到抑制，且与CaM无关。在肝细胞膜中，Ca2+和/或CaM不会改变腺苷酸环化酶活性。这些结果表明，生理浓度的Ca2+对腺苷酸环化酶活性的影响范围从CaM依赖性的活性刺激到无影响，再到CaM非依赖性的活性抑制。Ca2+对腺苷酸环化酶的作用可能是导致在cAMP生成系统和Ca(2+)动员系统之间所见的各种协同或拮抗相互作用的主要因素。
