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

TitlePharmacological modulation of the CO/HCO/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase.
Publication TypeJournal Article
Year of Publication2018
AuthorsWiggins SV, Steegborn C, Levin LR, Buck J
JournalPharmacol Ther
Volume190
Pagination173-186
Date Published2018 10
ISSN1879-016X
KeywordsAdenosine 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.

DOI10.1016/j.pharmthera.2018.05.008
Alternate JournalPharmacol. Ther.
PubMed ID29807057
PubMed Central IDPMC6484840
Grant ListUL1 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