Regulation of cardiovascular development by adenosine and adenosine-mediated embryo protection.
Regulation of cardiovascular development by adenosine and adenosine-mediated embryo protection.
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DOI：
10.1161/atvbaha.111.226811
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Wendler CC
中科院分区：
文献类型：
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作者：
Rivkees SA;Wendler CC
很少有信号分子像核苷腺苷那样有可能影响发育中的哺乳动物。随着组织缺氧和炎症，腺苷水平迅速增加。腺苷拮抗剂包括甲基黄嘌呤、咖啡因和茶碱。转导腺苷作用的受体是A1、A2a、A2b和A3腺苷受体(AR)。我们研究了腺苷是如何通过A1AR影响胚胎发育的。转基因小鼠与胚胎培养一起进行了研究。缺乏A1AR的胚胎在宫内低氧暴露后生长明显迟缓。对心脏中选择性缺乏A1AR的小鼠的研究发现，心脏是腺苷胚胎保护作用的关键部位。对分离胚胎的研究表明，腺苷在调节胚胎心脏功能方面起着关键作用，特别是在缺氧的情况下。当怀孕的小鼠在胚胎发育期间被腺苷拮抗剂咖啡因处理时，成年小鼠的心脏功能出现异常。腺苷通过A1AR发挥作用，在保护胚胎免受宫内压力方面发挥重要作用，而腺苷拮抗剂，包括咖啡因，可能是胚胎不受欢迎的暴露。
Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists include the methlyxanthines caffeine and theophylline. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined how adenosine acts via A1ARs to influence embryo development. Transgenic mice were studied along with embryo cultures. Embryos lacking A1ARs were markedly growth retarded following intrauterine hypoxia exposure. Studies of mice selectively lacking A1AR in the heart identify the heart as a key site of adenosines embryo protective effects. Studies of isolated embryos showed that adenosine plays a key role in modulating embryo cardiac function, especially in the setting of hypoxia. When pregnant mice were treated during embryogenesis with the adenosine antagonist caffeine, adult mice had abnormal heart function. Adenosine acts via A1ARs to play an essential role in protecting the embryo against intra uterine stress, and adenosine antagonists, including caffeine, may be an unwelcome exposure for the embryo.