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MODULATION OF ERYTHROPOIETIN PRODUCTION BY SELECTIVE ADENOSINE AGONISTS AND ANTAGONISTS IN NORMAL AND ANEMIC RATS

机译:正常和贫血大鼠中选择性腺苷激动剂和拮抗剂对红细胞生成素的调节

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Hypoxia or anemia is the fundamental stimulus for erythropoietin (EPO) production. Recent in vitro studies suggest that EPO secretion in response to hypoxia is regulated by adenosine in the kidney. In order to examine the in vivo effect of adenosine on EPO production, we determined the effects of adenosine receptor agonists and antagonists on serum EPO concentration in normal and anemic rats. In normal rats, intravenous injection of adenosine agonists (NECA, CHA and CGS-21680) dose-dependently stimulated EPO production. Pretreatment with KW-3902, an adenosine A1 antagonist with modest A2b antagonistic action, or KF17837, an adenosine A2a antagonist, inhibited the NECA (0.1 mg/kg, i.v.)-stimulated EPO production. Anemic hypoxia, induced by 2% (v/w body weight) blood withdrawal, increased serum EPO concentration from 38 +/- 2 to 352 +/- 76 mU/ml, with the increased serum adenosine concentration in the renal vein. KF17837 (0.1 mg/kg, i.v.), but not KW-3902 (0.1 mg/kg, i.v.), inhibited the anemic hypoxia-induced increase in EPO production. The present findings support the notion that adenosine mediates the EPO production in response to hypoxia in the kidney. [References: 34]
机译:缺氧或贫血是促红细胞生成素(EPO)生产的基本刺激。最近的体外研究表明,响应缺氧的EPO分泌受到肾脏腺苷的调节。为了检查体内腺苷对EPO产生的影响,我们确定了腺苷受体激动剂和拮抗剂对正常和贫血大鼠血清EPO浓度的影响。在正常大鼠中,静脉注射腺苷激动剂(NECA,CHA和CGS-21680)剂量依赖性地刺激EPO的产生。用具有适度A2b拮抗作用的腺苷A1拮抗剂KW-3902或腺苷A2a拮抗剂KF17837预处理可抑制NECA(0.1 mg / kg,i.v.)刺激的EPO产生。由2%(v / w体重)抽血引起的贫血性缺氧使血清EPO浓度从38 +/- 2增加到352 +/- 76 mU / ml,同时肾静脉中的血清腺苷浓度增加。 KF17837(0.1 mg / kg,i.v.)而非KW-3902(0.1 mg / kg,i.v.)抑制了贫血性缺氧引起的EPO产量增加。目前的发现支持腺苷介导对肾脏缺氧的EPO产生的观点。 [参考:34]

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