Ishikawa S, Higashiyama M, Kusaka I, Saito T, Nagasaka S, Fukuda S, Saito T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Nephron. 1997;76(2):208-14. doi: 10.1159/000190170.
The present study was undertaken to determine whether extracellular adenosine 5'-triphosphate (ATP) promotes cellular proliferation of cultured rat renal inner medullary collecting duct cells. Extracellular ATP increased inositol 1,4,5-triphosphate (IP3) production and cellular free calcium concentration - [Ca2+]i - in a dose-dependent manner. ATP also caused a transient cellular acidification. Extracellular ATP activated mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation in a dose-dependent manner. However, such effects were not obtained with adenosine 5'-diphosphate, adenosine monophosphate, and adenosine. In addition, uridine triphosphate, a P(2u) purinergic agonist, increased IP3 production and activated MAP kinase. 2-Methylthio ATP, a P(2y) purinergic agonist, also increased IP3 production, but did not affect the MAP kinase activity. We also examined the effect of arginine vasopressin on cellular growth. Arginine vasopressin did not alter MAP kinase activity and [3H]thymidine incorporation in cultured rat renal inner medullary collecting duct cells. These results indicate that extracellular ATP activates phospholipase C mediated through P(2u) and P(2y) purinergic receptors and promotes cellular proliferation mediated through P(2u) purinergic receptors in renal inner medullary collecting duct cells.
本研究旨在确定细胞外5'-三磷酸腺苷（ATP）是否能促进培养的大鼠肾内髓集合管细胞的增殖。细胞外ATP以剂量依赖性方式增加肌醇1,4,5-三磷酸（IP3）的产生和细胞内游离钙浓度 - [Ca2+]i - 。ATP还引起细胞短暂酸化。细胞外ATP以剂量依赖性方式激活丝裂原活化蛋白（MAP）激酶和[3H]胸苷掺入。然而，二磷酸腺苷、一磷酸腺苷和腺苷未获得此类效应。此外，P(2u)嘌呤能激动剂尿苷三磷酸增加IP3产生并激活MAP激酶。P(2y)嘌呤能激动剂2-甲硫基ATP也增加IP3产生，但不影响MAP激酶活性。我们还研究了精氨酸加压素对细胞生长的影响。精氨酸加压素不改变培养的大鼠肾内髓集合管细胞中的MAP激酶活性和[3H]胸苷掺入。这些结果表明，细胞外ATP通过P(2u)和P(2y)嘌呤能受体介导激活磷脂酶C，并通过P(2u)嘌呤能受体介导促进肾内髓集合管细胞的增殖。
