{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:36:46Z","timestamp":1781876206100,"version":"3.54.5"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,5]]},"abstract":"<jats:p>\n                    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\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    ). We cloned the sAC ortholog from the dogfish, a shark that regulates blood A\/B by absorbing and secreting protons (H\n                    <jats:sup>+<\/jats:sup>\n                    ) and HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    at its gills. Similar to mammalian sAC, dogfish soluble adenylyl cyclase (dfsAC) is activated by HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    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\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0911790107","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T22:19:27Z","timestamp":1260829167000},"page":"442-447","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":88,"title":["Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid\/base homeostasis"],"prefix":"10.1073","volume":"107","author":[{"given":"Martin","family":"Tresguerres","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;"},{"name":"Bamfield Marine Sciences Centre, Bamfield, BC V0R 1B0, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott K.","family":"Parks","sequence":"additional","affiliation":[{"name":"Bamfield Marine Sciences Centre, Bamfield, BC V0R 1B0, Canada; and"},{"name":"Department of Biological Sciences, University of Alberta, Edmonton, AB T5G 2E9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Salazar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonny R.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg G.","family":"Goss","sequence":"additional","affiliation":[{"name":"Bamfield Marine Sciences Centre, Bamfield, BC V0R 1B0, Canada; and"},{"name":"Department of Biological Sciences, University of Alberta, Edmonton, AB T5G 2E9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Buck","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,12,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1073\/pnas.96.1.79","article-title":"Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals","volume":"96","author":"Buck J","year":"1999","unstructured":"J Buck, ML Sinclair, L Schapal, MJ Cann, LR Levin, Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. 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