The A3 adenosine receptor attenuates the calcium rise triggered by NMDA receptors in retinal ganglion cells.
The A3 adenosine receptor attenuates the calcium rise triggered by NMDA receptors in retinal ganglion cells.
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DOI：
10.1016/j.neuint.2009.08.011
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发表时间：
2010-01
影响因子：
4.2
通讯作者：
Mitchell, Claire H.
中科院分区：
文献类型：
--
作者：
Zhang, Mei;Hu, Huiling;Zhang, Xiulan;Lu, Wennan;Lim, Jason;Eysteinsson, Thor;Jacobson, Kenneth A.;Laties, Alan M.;Mitchell, Claire H.
关键词：
A3腺苷受体正在成为神经元信号的重要调节因子，在某些情况下，受体刺激可以限制兴奋性。由于NMDA受体经常参与神经元的兴奋性，本研究考察了A3受体的激活是否会改变NMDA受体刺激引起的钙升高。钙水平是由分离的大鼠视网膜神经节细胞的fura-2成像确定的，因为这些神经元具有两种受体类型。短暂应用谷氨酸或NMDA可导致细胞内钙的可重复和可逆升高。A3激动剂Cl-IB-MECA降低了对谷氨酸和NMDA的反应。虽然腺苷模拟Cl-IB-MECA的作用，但A3受体拮抗剂MRS 1191阻碍了腺苷的阻断，暗示A3受体在对天然激动剂的反应中起作用。A1受体拮抗剂DPCPX提供了额外的抑制作用，这意味着A1和A3腺苷受体都有作用。新型A3激动剂MRS 3558 (1'S, 2'R, 3'S, 4'R, 5'S)-4-（2-氯-6-（3-氯苄胺）- 9h -嘌呤-9-基）-2,3-二羟基- n-甲基双环[3.1.0]]己烷-1-carboxamide和混合A1/A3激动剂MRS 3630 (1'S, 2'R, 3'S, 4'R, 5'S)-4-（2-氯-6-（环戊基胺）- 9h -嘌呤-9-基）-2,3-二羟基- n-甲基双环[3.1.0])- 1-carboxamide也抑制NMDA诱导的钙升高。低浓度的MRS 3558尤其有效，IC50为400pm。在所有病例中，A3受体刺激仅抑制30-50%的钙升高。综上所述，内源性或合成激动剂刺激A3腺苷受体都可以限制NMDA受体激活时钙的升高。A3受体激动剂部分阻断钙升高是否能改变下游对NMDA受体刺激的反应，这一点还有待确定。
The A3 adenosine receptor is emerging as an important regulator of neuronal signaling, and in some situations receptor stimulation can limit excitability. As the NMDA receptor frequently contributes to neuronal excitability, this study examined whether A3 receptor activation could alter the calcium rise accompanying NMDA receptor stimulation. Calcium levels were determined from fura-2 imaging of isolated rat retinal ganglion cells as these neurons possess both receptor types. Brief application of glutamate or NMDA led to repeatable and reversible elevations of intracellular calcium. The A3 agonist Cl-IB-MECA reduced the response to both glutamate and NMDA. While adenosine mimicked the effect of Cl-IB-MECA, the A3 receptor antagonist MRS 1191 impeded the block by adenosine, implicating a role for the A3 receptor in the response to the natural agonist. The A1 receptor antagonist DPCPX provided additional inhibition, implying a contribution from both A1 and A3 adenosine receptors. The novel A3 agonist MRS 3558 (1’S,2’R,3’S,4’R,5’S)-4-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0] hexane-1-carboxamide and mixed A1/A3 agonist MRS 3630 (1’S,2’R,3’S,4’R,5’S)-4-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0]hexane-1-carboxamide also inhibited the calcium rise induced by NMDA. Low levels of MRS 3558 were particularly effective, with an IC50 of 400 pM. In all cases, A3 receptor stimulation inhibited only 30-50% of the calcium rise. In summary, stimulation of the A3 adenosine receptor by either endogenous or synthesized agonists can limit the calcium rise accompanying NMDA receptor activation. It remains to be determined if partial block of the calcium rise by A3 agonists can modify downstream responses to NMDA receptor stimulation.
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体内再灌注后，A3腺苷受体和有丝分裂原激活的蛋白激酶在肺损伤中。
影响因子：
15.1
作者：
Matot, Idit;Weiniger, Carolyn F.;Zeira, Evelyne;Galun, Eithan;Joshi, Bhalchandra V.;Jacobson, Kenneth A.
通讯作者：
Jacobson, Kenneth A.
影响因子：
4.2
作者：
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通讯作者：
Osborne, Neville N.
影响因子：
7.3
作者：
Pugliese, AM;Latini, S;Pedata, F
通讯作者：
Pedata, F
影响因子：
5.8
作者：
Pugliese, Anna Maria;Coppi, Elisabetta;Pedata, Felicita
通讯作者：
Pedata, Felicita
影响因子：
4.2
作者：
Chen, Guann-Juh;Harvey, Brandon K.;Wang, Yun
通讯作者：
Wang, Yun