Bogdanov Y D, Dale L, King B F, Whittock N, Burnstock G
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
J Biol Chem. 1997 May 9;272(19):12583-90. doi: 10.1074/jbc.272.19.12583.
Extracellular ATP functions as a neurotransmitter and neuromodulator in the adult nervous system, and a signaling molecule in non-neural tissue, acting either via ligand-gated ion channels (P2X) or G-protein-coupled receptors (P2Y). ATP can cause an increase in intracellular Ca2+ (Ca2+i) in embryonic cells and so regulate cell proliferation, migration, and differentiation. We have isolated a Xenopus cDNA encoding a novel P2Y receptor, XlP2Y, which is expressed abundantly in developing embryos. Recombinant XlP2Y responds equally to all five naturally occurring nucleoside triphosphates (ATP, UTP, CTP, GTP, and ITP), which elicit a biphasic Ca2+-dependent Cl- current (ICl,Ca) where the second phase persists for up to 60 min. XlP2Y also causes a continuous release of Ca2+i and a low level persistent activation of ICl,Ca in Xenopus oocytes through the spontaneous efflux of ATP. mRNAs for XlP2Y are expressed transiently in the neural plate and tailbud during Xenopus development, coincident with neurogenesis. This restricted pattern of expression and novel pharmacological features confer unique properties to XlP2Y, which may play a key role in the early development of neural tissue.
细胞外ATP在成体神经系统中作为神经递质和神经调质发挥作用,在非神经组织中作为信号分子,通过配体门控离子通道(P2X)或G蛋白偶联受体(P2Y)起作用。ATP可使胚胎细胞内的细胞内Ca2+(Ca2+i)增加,从而调节细胞增殖、迁移和分化。我们分离出了非洲爪蟾的一个编码新型P2Y受体XlP2Y的cDNA,该受体在发育中的胚胎中大量表达。重组XlP2Y对所有五种天然存在的核苷三磷酸(ATP、UTP、CTP、GTP和ITP)的反应相同,这些核苷三磷酸会引发双相Ca2+依赖性Cl-电流(ICl,Ca),其中第二阶段可持续长达60分钟。XlP2Y还通过ATP的自发外流导致非洲爪蟾卵母细胞中Ca2+i的持续释放和ICl,Ca的低水平持续激活。在非洲爪蟾发育过程中,XlP2Y的mRNA在神经板和尾芽中短暂表达,与神经发生同时出现。这种受限的表达模式和新颖的药理学特性赋予了XlP2Y独特的性质,其可能在神经组织的早期发育中起关键作用。