ZM241385 is an antagonist of the facilitatory responses produced by the A(2A) adenosine receptor agonists CGS21680 and HENECA in the rat hippocampus
ZM241385 is an antagonist of the facilitatory responses produced by the A(2A) adenosine receptor agonists CGS21680 and HENECA in the rat hippocampus
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DOI：
10.1038/sj.bjp.0701507
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发表时间：
1997-12-01
影响因子：
7.3
通讯作者：
Ribeiro, JA
中科院分区：
文献类型：
--
作者：
Cunha, RA;Constantino, MD;Ribeiro, JA
在本研究中，我们研究了最近引入的非黄嘌呤a （2A）受体拮抗剂ZM241385（4-（2-氨基-2- 2-(2-呋喃基{1,2,4)-三唑{2,3-a{1,3,5}三嗪基-5-酰基氨基乙基）苯酚）取代典型a （2A）腺苷受体激动剂[H-3]CGS21680（2-[4-（2-对羧基乙基）苯胺]-5'- n-乙基羧氨基腺苷）的结合能力，并改变由a （2A）选择性激动剂引起的促进反应。CGS21680和HENECA（2-己炔-5′- n -乙基羧氨基腺苷）在大鼠海马中的作用ZM241385对[H-3]CGS21680结合海马（K-i为0.52 nM）和纹状体膜（K-i为0.35 nM）的置换作用几乎相同，而HENECA对[H-3]CGS21680结合纹状体（K-i为4.5 nM）的置换作用比海马膜（K-i为19 nM）的置换作用更有效HENECA （3 ~ 30 nM）与CGS21680在促进左旋碱诱导的[H-3]乙酰胆碱从过度使用的海马突触体释放方面具有同等的促进作用，ZM241385 （20 nM）抑制HENECA （30 nM）和CGS21680 （30 nM）的促进作用；这种拮抗作用被250 nM的CSC所模拟相比之下，CGS21680 （10-30 nM）比HENECA （10-30 nM）更能促进海马Schaffer纤维/CAl锥体突触的突触传递，并且CGS21680 （10 nM）的促进作用被ZM241385 （20 nM）阻断，而CSC （250 nM）使CGS21680诱导的促进作用减弱40%这些结果表明，ZM241385是第一个具有同等效力的A（2A）拮抗剂，可以取代[3H]CGS21680结合到纹状体和边缘区域，并且可以在海马中以一般的效率拮抗HENECA或CGS21680介导的促进反应。
1 In the present study, we investigated the ability of a recently introduced non-xanthine A(2A) receptor antagonist, ZM241385 (4-(2-[7-amino-2-(2-furyl{1,2,4)-triazolo{2,3-a{1,3,5}triazin-5-yl-aminoethyl)phenol) to displace binding of the prototypical A(2A) adenosine receptor agonist [H-3]CGS21680 (2-[4-(2-p-carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine) and to modify the facilitatory responses caused by the A(2A) selective agonists, CGS21680 and HENECA (2-hexynl-5'-N-ethylcarboxamidoadenosine) in rat hippocampal preparations.2 ZM241385 was nearly equipotent to displace [H-3]CGS21680 (30 nM) binding to hippocampal (K-i of 0.52 nM) and to striatal membranes (K-i of 0.35 nM), whereas HENECA was a more potent displacer of [H-3]CGS21680 binding to striatal (K-i of 4.5 nM) than to hippocampal membranes (K-i of 19 nM).3 HENECA (3-30 nM) was equipotent with CGS21680 to facilitate veratridine-evoked [H-3]acetylcholine release from superfused hippocampal synaptosomes and ZM241385 (20 nM) inhibited the facilitatory effects of both HENECA (30 nM) and CGS21680 (30 nM); this antagonism was mimicked by CSC (250 nM).4 In contrast, CGS21680 (10-30 nM) was more potent than HENECA (10-30 nM) to facilitate synaptic transmission in Schaffer fibres/CAl pyramid synapses of hippocampal slices and the facilitatory effect of CGS21680 (10 nM) was blocked by ZM241385 (20 nM) whereas CSC (250 nM) caused a 40% attenuation of this CGS21680-induced facilitation.5 These results indicate that ZM241385 is the first A(2A) antagonist with equal potency to displace [3H]CGS21680 binding to striatal and limbic regions, and with general efficiency to antagonize HENECA- or CGS21680-mediated facilitatory responses in the hippocampus.