Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis Academic Article uri icon


MeSH Major

  • Acid-Base Equilibrium
  • Adenylyl Cyclases
  • Bicarbonates
  • Homeostasis


  • pH homeostasis is essential for life, yet it remains unclear how animals sense their systemic acid/base (A/B) status. Soluble adenylyl cyclase (sAC) is an evolutionary conserved signaling enzyme that produces the second messenger cAMP in response to bicarbonate ions (HCO(3)(-)). We cloned the sAC ortholog from the dogfish, a shark that regulates blood A/B by absorbing and secreting protons (H(+)) and HCO(3)(-) at its gills. Similar to mammalian sAC, dogfish soluble adenylyl cyclase (dfsAC) is activated by HCO(3)(-) and can be inhibited by two structurally and mechanistically distinct small molecule inhibitors. dfsAC is expressed in the gill epithelium, where the subset of base-secreting cells resides. Injection of inhibitors into animals under alkaline stress confirmed that dfsAC is essential for maintaining systemic pH and HCO(3)(-) levels in the whole organism. One of the downstream effects of dfsAC is to promote the insertion of vacuolar proton pumps into the basolateral membrane to absorb H(+) into the blood. sAC orthologs are present throughout metazoans, and mammalian sAC is expressed in A/B regulatory organs, suggesting that systemic A/B sensing via sAC is widespread in the animal kingdom.

publication date

  • February 15, 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2806762

Digital Object Identifier (DOI)

  • 10.1073/pnas.0911790107

PubMed ID

  • 20018667

Additional Document Info

start page

  • 442

end page

  • 7


  • 107


  • 1