Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis

Martin Tresguerres, Scott K. Parks, Eric Salazar, Lonny R. Levin, Greg G. Goss, Jochen Buck

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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 (HCO3-). We cloned the sAC ortholog from the dogfish, a shark that regulates blood A/B by absorbing and secreting protons (H+) and HCO3- at its gills. Similar to mammalian sAC, dogfish soluble adenylyl cyclase (dfsAC) is activated by HCO3- 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 HCO3 - 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.

Original languageEnglish (US)
Pages (from-to)442-447
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Dogfish
  • Gill
  • Proton pump
  • cAMP
  • pH

ASJC Scopus subject areas

  • General

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