Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 107 (2009-12-19), Heft 1
Online
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Zugriff:
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.
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Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis
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Autor/in / Beteiligte Person: | Tresguerres, Martin ; Parks, Scott K. ; Goss, Greg G. ; Levin, Lonny R. ; Salazar, Eric ; Buck, Jochen |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 107 (2009-12-19), Heft 1 |
Veröffentlichung: | 2009 |
Medientyp: | unknown |
ISSN: | 1091-6490 (print) |
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