Title | Pharmacological modulation of the CO/HCO/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Wiggins SV, Steegborn C, Levin LR, Buck J |
Journal | Pharmacol Ther |
Volume | 190 |
Pagination | 173-186 |
Date Published | 2018 10 |
ISSN | 1879-016X |
Keywords | Adenosine Triphosphate, Adenylyl Cyclases, Animals, Bicarbonates, Calcium, Carbon Dioxide, Cyclic AMP, Drug Development, Humans, Hydrogen-Ion Concentration, Phosphoric Diester Hydrolases |
Abstract | 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 CO/HCO/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. |
DOI | 10.1016/j.pharmthera.2018.05.008 |
Alternate Journal | Pharmacol. Ther. |
PubMed ID | 29807057 |
PubMed Central ID | PMC6484840 |
Grant List | UL1 RR024996 / RR / NCRR NIH HHS / United States R01 GM107442 / GM / NIGMS NIH HHS / United States R01 HD088571 / HD / NICHD NIH HHS / United States R21 EY025810 / EY / NEI NIH HHS / United States R01 GM062328 / GM / NIGMS NIH HHS / United States R01 AG061290 / AG / NIA NIH HHS / United States |