ATP inhibits glutamate synaptic release by acting at P2Y receptors in pyramidal neurons of hippocampal slices.
ATP inhibits glutamate synaptic release by acting at P2Y receptors in pyramidal neurons of hippocampal slices.
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发表时间：
2000-04
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通讯作者：
V. Mendoza-Fernández;R. Andrew;C. Barajas-López
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作者：
V. Mendoza-Fernández;R. Andrew;C. Barajas-López
已经提出，细胞外ATP抑制突触释放谷氨酸从海马CA 1突触后，其catenorization腺苷。我们调查的可能性，至少有一部分的这种效果是由ATP本身介导的P2 Y受体的作用。ATP和各种类似物降低谷氨酸介导的兴奋性突触后电位的振幅和持续时间在所有测试的神经元。这种作用是可逆的，并且具有浓度依赖性，并且具有以下激动剂效力的等级顺序：AMP = ATP =腺苷-5 '-O-（3-硫代）三磷酸>腺苷= ADP。α，β-亚甲基ATP、β，γ-亚甲基ATP、2-甲硫基腺苷5 '-三磷酸、GTP和UTP仅诱导部分应答。由外源性谷氨酸引起的去极化不受ATP的影响，表明这种核苷酸的行为突触前抑制谷氨酸介导的兴奋性突触后电位。用α，β-亚甲基ADP、苏拉明或磷酸哒嗪-6-偶氮苯基-2 '，4'-二磺酸4-钠抑制外核苷酸酶活性，或去除细胞外腺苷（用腺苷脱氨酶），都不会改变ATP效应。8-环戊基茶碱竞争性抑制ATP效应，而P2受体拮抗剂（磷酸哒嗪-6-偶氮苯基-2 '，4'-二磺酸4-钠，苏拉明和活性蓝2）无效。ATP的作用对百日咳毒素（PTX）的敏感性远高于腺苷。PTX后，腺苷-5 '-O-（3-硫代）三磷酸仅诱导部分反应，ATP浓度-反应曲线呈双相。该曲线的第二阶段被腺苷脱氨酶阻断，这意味着它是由腺苷介导的ATP催化的结果。然而，在控制条件下，ATP的催化剂不需要解释其作用。总之，ATP通过直接激活PTX和8-环戊基茶碱敏感的P2 Y受体来抑制谷氨酸的突触释放。
It has been proposed that extracellular ATP inhibits synaptic release of glutamate from hippocampal CA1 synapses after its catabolism to adenosine. We investigated the possibility that at least part of this effect is mediated by ATP itself acting on P2Y receptors. ATP and various analogs decreased the amplitude and duration of glutamate-mediated excitatory postsynaptic potentials in all tested neurons. This effect was reversible and concentration-dependent and had the following rank order of agonist potency: AMP = ATP = adenosine-5'-O-(3-thio)triphosphate > adenosine = ADP. alpha,beta-Methylene ATP, beta,gamma-methylene ATP, 2-methylthioadenosine 5'-triphosphate, GTP, and UTP induced only a partial response. The depolarization induced by exogenous glutamate was not affected by ATP, indicating that this nucleotide acts presynaptically to inhibit glutamate-mediated excitatory postsynaptic potentials. Neither inhibition of ectonucleotidase activity with alpha,beta-methylene ADP, suramin, or pyridaxalphosphate-6-azophenyl-2',4'-disulfonic acid 4-sodium nor removal of extracellular adenosine (with adenosine deaminase) altered ATP effects. 8-Cyclopentyltheophylline competitively inhibited ATP effects, whereas P2 receptor antagonists (pyridaxalphosphate-6-azophenyl-2',4'-disulfonic acid 4-sodium, suramin, and reactive blue 2) were ineffective. ATP effects were by far more sensitive to pertussis toxin (PTX) than those of adenosine. After PTX, adenosine-5'-O-(3-thio)triphosphate induced only a partial response, and ATP concentration-response curve was biphasic. The second phase of this curve was blocked by adenosine deaminase, implying that it is mediated by adenosine as a result of ATP catabolism. Under control conditions, however, catabolism of ATP is not required to explain its actions. In conclusion, ATP inhibits synaptic release of glutamate by direct activation of P2Y receptors that are PTX- and 8-cyclopentyltheophylline-sensitive.