Grubb B D, Evans R J
Department of Cell Physiology & Pharmacology, University of Leicester, UK.
Eur J Neurosci. 1999 Jan;11(1):149-54. doi: 10.1046/j.1460-9568.1999.00426.x.
P2X receptors for adenosine 5'-triphosphate (ATP) comprise a family of ligand-gated cation channels with distinct characteristics which are dependent on the receptor subunits (P2X1-7) expressed, and the homomeric or heteromeric assembly of protein subunits in individual cells. We describe the properties of P2X receptors expressed by cultured adult rat dorsal root ganglion cells on the basis of the time course of responses to ATP, alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-meATP) and 2-methyl-thioadenosine 5'-triphosphate (2-meSATP), and using the antagonists 2',3'-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP), a novel and highly selective purinoceptor antagonist, suramin and iso-pyridocalphosphate-6-azophenyl-2',5' disulphonic acid (PPADS). ATP (10 microM) evoked inward currents in approximately 95% of neurons tested and > 80% responded with a fast transient inward current that rapidly inactivated during the continued presence of ATP. Of the remaining neurons, approximately 4% showed a sustained response and approximately 10% showed a combination of transient and sustained components. Rapid application of ATP, alpha,beta-meATP and 2meSATP demonstrated these to be full agonists of the rapidly inactivating P2X receptor (pA50 values = 5.83, 5.86 and 5.55, respectively), whilst uridine triphosphate (UTP) and 1-beta,gamma-methyleneadenosine 5'-triphosphate (1-beta,gamma-meATP) were ineffective as agonists. These rapidly inactivating responses could be inhibited by TNP-ATP, suramin and PPADS (pIC50 = 9.5, 6.5, 6.4, respectively). Using inactivation protocols, we demonstrate the presence of homomeric P2X3-like receptors and non-inactivating P2X receptors, which indicates that individual subsets of adult dorsal root ganglion neurons have distinct P2X receptor phenotypes, and that individual DRG neurons may express multiple P2X receptor subtypes.
三磷酸腺苷（ATP）的P2X受体是一类配体门控阳离子通道家族，具有不同的特性，这些特性取决于所表达的受体亚基（P2X1 - 7）以及单个细胞中蛋白质亚基的同聚体或异聚体组装。我们根据对ATP、α,β - 亚甲基三磷酸腺苷（α,β - meATP）和2 - 甲基硫代三磷酸腺苷（2 - meSATP）的反应时间进程，并使用拮抗剂2',3' - O -（2,4,6 - 三硝基苯基）ATP（TNP - ATP，一种新型且高度选择性的嘌呤受体拮抗剂）、苏拉明和异 - 吡啶基焦磷酸 - 6 - 偶氮苯基 - 2',5' - 二磺酸（PPADS），描述了培养的成年大鼠背根神经节细胞所表达的P2X受体的特性。ATP（10 μM）在大约95%的测试神经元中诱发内向电流，超过80%的神经元以快速瞬态内向电流做出反应，该电流在ATP持续存在期间迅速失活。在其余神经元中，约4%表现出持续反应，约10%表现出瞬态和持续成分的组合。快速施加ATP、α,β - meATP和2 - meSATP表明它们是快速失活的P2X受体的完全激动剂（pA50值分别为5.83、5.86和5.55），而三磷酸尿苷（UTP）和1 - β,γ - 亚甲基腺苷5' - 三磷酸（1 - β,γ - meATP）作为激动剂无效。这些快速失活的反应可被TNP - ATP、苏拉明和PPADS抑制（pIC50分别为9.5、6.5、6.4）。使用失活方案，我们证明了同聚体P2X3样受体和非失活P2X受体的存在，这表明成年背根神经节神经元的各个亚群具有不同的P2X受体表型，并且单个背根神经节神经元可能表达多种P2X受体亚型。
