Department of Pharmacology, Weill Cornell Medical College, New York, New York.
J Pharmacol Exp Ther. 2013 Dec;347(3):589-98. doi: 10.1124/jpet.113.208496. Epub 2013 Oct 3.
The second messenger cAMP is involved in a number of cellular signaling pathways. In mammals, cAMP is produced by either the hormonally responsive, G protein-regulated transmembrane adenylyl cyclases (tmACs) or by the bicarbonate- and calcium-regulated soluble adenylyl cyclase (sAC). To develop tools to differentiate tmAC and sAC signaling, we determined the specificity and potency of commercially available adenylyl cyclase inhibitors. In cellular systems, two inhibitors, KH7 and catechol estrogens, proved specific for sAC, and 2',5'-dideoxyadenosine proved specific for tmACs. These tools provide a means to define the specific contributions of the different families of adenylyl cyclases in cells and tissues, which will further our understanding of cell signaling.
第二信使 cAMP 参与了许多细胞信号通路。在哺乳动物中，cAMP 要么由激素反应性、G 蛋白调节的跨膜腺苷酸环化酶（tmAC）产生，要么由碳酸氢盐和钙调节的可溶性腺苷酸环化酶（sAC）产生。为了开发区分 tmAC 和 sAC 信号的工具，我们确定了商业可获得的腺苷酸环化酶抑制剂的特异性和效力。在细胞系统中，两种抑制剂 KH7 和儿茶酚雌激素被证明对 sAC 具有特异性，而 2'，5'-二脱氧腺苷则对 tmACs 具有特异性。这些工具为定义不同家族的腺苷酸环化酶在细胞和组织中的特定贡献提供了一种手段，这将进一步加深我们对细胞信号转导的理解。
