Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen-glucose deprivation episodes of different duration
Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen-glucose deprivation episodes of different duration
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DOI：
10.1016/j.bcp.2007.06.003
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发表时间：
2007-09-01
影响因子：
5.8
通讯作者：
Pedata, Felicita
中科院分区：
文献类型：
--
作者：
Pugliese, Anna Maria;Coppi, Elisabetta;Pedata, Felicita
通过氧和葡萄糖剥夺（OGD），研究了大鼠海马切片在严重（7分钟）和较短（2-5分钟）缺血条件下腺苷A(3)受体在突触传递中的作用。研究了选择性A(3)激动剂或拮抗剂对CA1锥体区树突水平细胞外记录的场兴奋性突触后电位（fepps）的影响。新型选择性A(3)拮抗剂LJ1251 (（2R,3R,4S)-2-（2-氯-6-（3-碘苯氨基）- 9h -嘌呤-9-基）四氢噻吩-3,4-二醇，0.1-10 nM）保护海马片免受严重OGD诱导的不可逆fEPSP抑制，并阻止或延迟缺氧去极化的出现。当严重OGD时，也得到了类似的结果，受体脱敏暴露于各种选择性a(3)激动剂：5'- n -甲基羧氨基腺苷衍生物cl - b - meca （N-6-（3-碘苄基）-2-氯），VT72 （N-6-甲氧基-2-苯乙基），VT158 （N-6-甲氧基-2-苯乙基），VT160 （N-6-甲氧基-2-（2-吡啶基）-乙基），VT163 （N-6-甲氧基-2-对乙酰苯乙基）和AR132 （N-6-甲基-2-苯乙基腺苷）。选择性A(3)拮抗剂MRS1523（3 -丙基-6-乙基- 5-[（乙基硫）羰基]-2 -苯基-4-丙基-3-吡啶羧酸盐，100 nM）可减轻OGD 2 min引起的fEPSP抑制，并在OGD 5 min后更快恢复fEPSP振幅。在每一种A(3)激动剂存在的情况下，2或5分钟的OGD也得到了类似的结果。短时间暴露于A(3)激动剂显著延迟了OGD 5min后fEPSP振幅的恢复。这表明，在选择性A(3)激动剂的刺激下，A(3)受体在OGD期间经历脱敏。推测CA1海马A(3)受体在短暂缺血（2和5 min）时释放的腺苷刺激下可能对神经传递起到A(1)样的保护作用。严重缺血会使A(3)受体介导的作用由保护作用转变为损伤作用。
The role of adenosine A(3) receptors in synaptic transmission under severe (7 min) and shorter (2-5 min) ischemic conditions, obtained by oxygen and glucose deprivation (OGD), was investigated in rat hippocampal slices. The effects of selective A(3) agonists or antagonists were examined on field excitatory postsynaptic potentials (fEPSPs) extracellularly recorded at the dendritic level of the CA1 pyramidal region. The novel, selective A(3) antagonist LJ1251 ((2R,3R,4S)-2-(2-chloro-6-(3-iodobenzylamino)-9H-purin-9-yl)tetrahydrothiophene-3,4-diol, 0.1-10 nM) protected hippocampal slices from irreversible fEPSP depression induced by severe OGD and prevented or delayed the appearance of anoxic depolarization. Similar results were obtained when severe OGD was carried out with a long, receptor- desensitizing exposure to various selective A(3) agonists: 5'-N-methylcarboxamidoadenosine derivatives Cl-IB-MECA (N-6-(3-iodobenzyl)-2-chloro), VT72 (N-6-methoxy-2phenylethynyl), VT158 (N-6-methoxy-2-phenylethynyl), VT160 (N-6-methoxy-2-(2-pyridinyl)-ethynyl), and VT163 (N-6-methoxy-2-p-acetylphenylethynyl) and AR132 (N-6-methyl-2-phenylethynyladenosine).The selective A(3) antagonist MRS1523 (3 -propyl-6- ethyl- 5 - [(ethylthio) carbonyl] -2 -phenyl-4-propyl-3-pyridine carboxylate, 100 nM) reduced fEPSP depression evoked by 2-min OGD and induced a faster recovery of fEPSP amplitude after 5-min OGD. Similar results were obtained for 2- or 5-min OGD applied in the presence of each of the A(3) agonists tested. Shorter exposure to A(3) agonists significantly delayed the recovery of fEPSP amplitude after 5min OGD.This indicates that A(3) receptors, stimulated by selective A(3) agonists, undergo desensitization during OGD. It is inferred that CA1 hippocampal A(3) receptors stimulated by adenosine released during brief ischemia (2 and 5 min) might exert A(1)-like protective effects on neuro-transmission. Severe ischemia would transform the A(3) receptor-mediated effects from protective to injurious.