Adenosine A1 and A3 receptors mediate inhibition of synaptic transmission in rat cortical neurons
Adenosine A1 and A3 receptors mediate inhibition of synaptic transmission in rat cortical neurons
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DOI：
10.1016/s0028-3908(00)00117-9
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发表时间：
2001-01-01
影响因子：
4.7
通讯作者：
Nieber, K
中科院分区：
文献类型：
--
作者：
Brand, A;Vissiennon, Z;Nieber, K
为了表征选择性腺苷A（1）和A（3）受体配体对突触神经传递的作用，在含有联合额叶皮质锥体细胞的大鼠脑切片制备物中进行了细胞内记录。选择性A（1）受体激动剂N-6-环戊基腺苷（CPA）浓度依赖性地抑制局灶电刺激诱发的兴奋性突触后电位（PSP）。CPA介导的抑制作用可被高度A（1）受体选择性拮抗剂1，3-二丙基-8-环戊基黄嘌呤（DPCPX）阻断。A（3）受体激动剂N-6-（3-碘苄基）-腺苷-5 '-N-甲基甲酰胺（IB-MECA）浓度依赖性地抑制诱发的PSP，而A（1）受体则被DPCPX持续阻断。在此条件下，A（3）受体拮抗剂9-氯-2-（2-呋喃基）-5-[（苯乙酰基）氨基]-1，2，4-三唑并[1，5-c]喹唑啉（MRS 1220）对PSP无影响，但可完全抑制IB-MECA的作用。IB-MECA的抑制作用不受DPCPX的影响。CPA在IB-MECA后应用时还抑制了PSP。PSP的N-甲基-D-天冬氨酸（NMDA）和非NMDA受体成分的药理学解离表明，CPA以及IB-MECA减少两者。我们的结论是腺苷A（1）和A（3）受体存在于皮质锥体细胞上，并参与兴奋性神经传递的抑制。我们的研究结果表明两种受体亚型之间没有相互作用。单独的抑制作用可能在存在高水平内源性释放的腺苷的情况下变得特别明显，如在缺氧中所见。(C)2000爱思唯尔科技有限公司版权所有。
Intracellular recordings were made in rat brain slice preparations containing pyramidal cells of the associative frontal cortex in order to characterize the action of selective adenosine A(1) and A(3) receptor ligands on synaptic neurotransmission. The selective A(1) receptor agonist N-6-cyclopentyladenosine (CPA) inhibited concentration-dependently the excitatory postsynaptic potentials (PSPs) which were evoked by focal electrical stimulation. The CPA-mediated inhibition was blocked by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly A(1) receptor-selective antagonist. The A(3) receptor agonist N-6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) inhibited concentration-dependently the evoked PSPs while the A(1) receptors were blocked continuously by DPCPX. Under these conditions, the A(3) receptor antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino]-1,2,4-triazolo[1,5-c]quinazoline (MRS 1220) did not influence the PSPs but inhibited completely the effect of IB-MECA. The inhibitory effect of IB-MECA, was unaffected by DPCPX. CPA additionally inhibited the PSPs when applied after IB-MECA. Pharmacological dissociation of the N-methyl-D-aspartate (NMDA) and non-NMDA receptor components of the PSPs showed that CPA as well as IB-MECA reduced both. We conclude that adenosine A(1) and A(3) receptors are present on cortical pyramidal cells and involved in the inhibition of excitatory neurotransmission. Our results indicate no interplay between the two receptor subtypes. The separate inhibition may become particularly evident in situations where there are high levels of endogenously released adenosine, as seen in hypoxia. (C) 2000 Elsevier Science Ltd. All rights reserved.