Pharmacological modulation of the CO(2)/HCO(3)(-)/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase.

Pharmacological modulation of the CO(2)/HCO(3)(-)/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase.
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CO(2)/HCO(3)( - )/pH-,钙 - 和ATP传感可溶性腺苷酸环化酶的药理调节。

DOI:
10.1016/j.pharmthera.2018.05.008
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发表时间:
2018-10
影响因子:
13.5
通讯作者:
Buck J
Buck J
中科院分区:
医学1区
文献类型:
--
作者:
Wiggins SV;Steegborn C;Levin LR;Buck J

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环AMP (cAMP)是典型的第二信使,涉及多种(通常是相反的)生理过程。它同时介导多个不同的过程,通常在单个细胞内,通过在独立调节和空间限制的微域内局部作用。在每个微结构域内,cAMP的水平取决于腺苷酸环化酶合成和磷酸二酯酶(PDEs)降解之间的平衡。在哺乳动物细胞中,有许多PDE异构体和两种类型的腺苷酸环化酶;G蛋白调节跨膜腺苷酸环化酶(tmac)和CO2//pH、钙和atp敏感的可溶性腺苷酸环化酶(sAC)。鉴别单个环核苷酸微域的作用需要对各种pde和/或腺苷酸环化酶有选择性的药理学调节剂。这些工具为开发针对个体cAMP依赖通路的治疗方法提供了机会。最近对tmac的药理学调节剂进行了综述,在这篇综述中,我们描述了目前可用于研究sAC的药理学工具的现状。
Cyclic AMP (cAMP), the prototypical second messenger, has been implicated in a wide variety of (often opposing) physiological processes. It simultaneously mediates multiple, diverse processes, often within a single cell, by acting locally within independently-regulated and spatially-restricted microdomains. Within each microdomain, the level of cAMP will be dependent upon the balance between its synthesis by adenylyl cyclases and its degradation by phosphodiesterases (PDEs). In mammalian cells, there are many PDE isoforms and two types of adenylyl cyclases; the G protein regulated transmembrane adenylyl cyclases (tmACs) and the CO2//pH-, calcium-, and ATP-sensing soluble adenylyl cyclase (sAC). Discriminating the roles of individual cyclic nucleotide microdomains requires pharmacological modulators selective for the various PDEs and/or adenylyl cyclases. Such tools present an opportunity to develop therapeutics specifically targeted to individual cAMP dependent pathways. The pharmacological modulators of tmACs have recently been reviewed, and in this review, we describe the current status of pharmacological tools available for studying sAC.
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