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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis
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Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis

机译：碳酸氢盐敏感的可溶性腺苷酸环化酶是酸/碱稳态的重要传感器

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摘要

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 baso-lateral 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.
机译：pH稳态对生命至关重要，但尚不清楚动物如何感觉其体内酸/碱（A / B）状态。可溶性腺苷酸环化酶（sAC）是一种进化保守的信号酶，可响应碳酸氢根离子（HCO_3-）产生第二个信使cAMP。我们从一条鲨鱼中克隆了sAC直系同源物，该鲨鱼通过在其g处吸收和分泌质子（H〜+）和HCO_3〜-来调节血液A / B。与哺乳动物sAC相似，dog鱼可溶性腺苷酸环化酶（dfsAC）被HCO_3激活，并可以被两种在结构和机制上不同的小分子抑制剂所抑制。 dfsAC在the上皮中表达，,分泌上皮细胞位于其中。在碱性胁迫下向动物体内注入抑制剂证实，dfsAC对于维持整个生物体内的全身pH和HCO_3〜-水平至关重要。 dfsAC的下游作用之一是促进液泡质子泵插入基底外侧膜以吸收H〜+进入血液。 sAC直系同源物存在于整个后生动物中，哺乳动物sAC在A / B调节器官中表达，这表明通过sAC进行的系统性A / B感测在动物界广泛存在。

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  • 作者

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

  • 作者单位

    Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065 Bamfield Marine Sciences Centre, Bamfield, BC VOR 1B0, Canada;

    Bamfield Marine Sciences Centre, Bamfield, BC VOR 1B0, Canada Department of Biological Sciences, University of Alberta, Edmonton, AB T5G 2E9, Canada;

    Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;

    Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;

    Bamfield Marine Sciences Centre, Bamfield, BC VOR 1B0, Canada Department of Biological Sciences, University of Alberta, Edmonton, AB T5G 2E9, Canada;

    Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cAMP; pH; proton pump dogfish; gill;

    机译：营;pH值质子泵狗鱼;鳃;

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