EVIDENCE FOR A ROLE OF PITUITARY ATP RECEPTORS IN THE REGULATION OF PITUITARY-FUNCTION
EVIDENCE FOR A ROLE OF PITUITARY ATP RECEPTORS IN THE REGULATION OF PITUITARY-FUNCTION
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DOI：
10.1073/pnas.92.11.5219
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发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
LIGHTMAN, SL
中科院分区：
文献类型：
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作者：
CHEN, ZP;KRATZMEIER, M;LIGHTMAN, SL
尽管在一些生物系统中，ATP作为细胞外介质的作用被迅速接受，但本报告显示ATP可能介导垂体细胞的生理反应。我们现在已经能够证明ATP受体的特定作用，介导促性腺激素的黄体生成素的释放，并结合进一步的研究，清楚地表明ATP可以从培养的大鼠垂体细胞中胞外释放。ATP和UTP （100 μ M）均能使过量细胞的黄体生成素释放率增加约14倍。腺苷5′-[α， β -亚甲基]三磷酸和5′-[β， γ -亚甲基]三磷酸无效，2-甲基硫代atp只有适度的刺激作用。UTP和ATP发生了同源和异源脱敏，但它们没有加性效应。因此，核苷酸可以通过一类ATP受体（P-2U亚型）有效刺激促黄体生成素的释放。钙离子载体A23187以浓度依赖性和Ca2+依赖性的方式激发垂体细胞释放大量ATP，并通过A23187预处理使其脱敏。这暗示了一种可能的旁分泌和/或自分泌机制，通过这种机制，核苷酸可能对垂体细胞发挥作用。总之，我们已经提供了强有力的证据，证明细胞外核苷酸作为垂体-特别是促性腺功能介质的新作用。
Despite a rapidly increasing acceptance for a role of ATP as an extracellular mediator in several biological systems, the present report shows that ATP may mediate physiological responses in pituitary cells. We have now been able to demonstrate a specific action of ATP receptors to mediate the release of luteinizing hormone from gonadotropes and have coupled them with further studies that clearly show that ATP can be exocytotically released from cultured rat pituitary cells. Both ATP and UTP (100 mu M) caused a >14-fold increase in the rate of luteinizing hormone release from superfused cells. Adenosine 5'-[alpha,beta-methylene]triphosphate and 5'-[beta,gamma-methylene]triphosphate were ineffective, and 2-methylthio-ATP had only a modest stimulatory effect. Homologous and heterologous desensitization occurred with UTP and ATP, and these did not have additive effects. Thus, nucleotides can be effective stimulators of luteinizing hormone release through a single class of ATP receptor (P-2U subtype). The calcium ionophore A23187 provoked release of a substantial amount of ATP from pituitary cells in a concentration- and Ca2+-dependent manner, which was desensitized by pretreatment with A23187. This implies a possible paracrine and/or autocrine mechanism by which nucleotides may exert their effects on pituitary cells. In conclusion, we have provided strong evidence for a novel role of extracellular nucleotides as mediators in pituitary-in particular, in gonadotrope-function.