A(1) and A(2A) adenosine receptors and A(1) mRNA in mouse brain: effect of long-term caffeine treatment
A(1) and A(2A) adenosine receptors and A(1) mRNA in mouse brain: effect of long-term caffeine treatment
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DOI：
10.1016/s0006-8993(97)00378-8
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发表时间：
1997-07-11
期刊：
影响因子：
2.9
通讯作者：
Fredholm, BB
中科院分区：
文献类型：
--
作者：
Johansson, B;Georgiev, V;Fredholm, BB
研究了口服咖啡因对小鼠脑中A（1）和A（2A）受体的影响，已知咖啡因的剂量可产生显著的适应性效应。向饮用水中加入咖啡因（0.1、0.3或1 g/l），并在14天给药期后处死动物。用定量放射自显影法研究了激动剂[H-3]环己基腺苷（CHA）和拮抗剂[H-3] 1，3-二丙基-8-环戊基黄嘌呤（DPCPX）与A（1）受体的配体结合。在放射自显影实验期间，咖啡因未残留在切片中。咖啡因治疗（1 g/l，但不是0.1或0.3 g/l）倾向于增加[H-3]CHA与海马CA 3子区的结合，但没有研究其他区域。由于[H-3]DPCPX与CA 3、大脑和小脑皮质的结合不受咖啡因处理的影响，因此A（1）受体的数量没有变化。同样，CHA取代[H-3]DPCPX结合的能力没有变化，这表明与G蛋白偶联的A（1）受体的比例没有重大变化。用原位杂交法测定的A（1）受体的mRNA，在所检查的结构中，咖啡因处理组和对照组小鼠之间没有显著差异。因此，较高剂量的咖啡因可引起A（1）激动剂结合的增加，而A（1）mRNA或A（1）拮抗剂结合没有相应的变化，这表明长期咖啡因治疗后观察到的适应性变化可能发生在不同于A（1）受体的部位。咖啡因（1 g/l）增加了纹状体中的A（2A）受体，测量为激动剂[H-3]CGS 21680的结合，表明A（2A）受体的上调可能是咖啡因摄入的适应性效应。(C)1997年Elsevier Science B.V.
The effect of oral treatment with caffeine, in doses that are known to produce marked adaptive effects, was investigated on A(1) and A(2A) receptors in the mouse brain. Caffeine (0.1, 0.3 or 1 g/l) was added to the drinking water and the animals were sacrificed after a 14-day treatment period. Ligand binding to A(1) receptors was studied, using quantitative autoradiography, with the agonist [H-3]cyclohexyladenosine (CHA) and the antagonist [H-3]1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Caffeine did not remain in the sections during the autoradiography experiments. Caffeine treatment (1 g/l, but not 0.1 or 0.3 g/l) tended to increase [H-3]CHA binding to the CA3 subfield of the hippocampus, but in no other region studied. There was no change in the number of A(1) receptors since [H-3]DPCPX binding to the CA3, cerebral and cerebellar cortex was not influenced by caffeine treatment. There was similarly no change in the ability of CHA to displace [H-3]DPCPX binding, suggesting that there are no major changes in the proportion of A(1) receptors that are coupled to G-proteins. mRNA for the A(1) receptor, measured by in situ hybridization, did not differ significantly between caffeine-treated and control mice in the structures examined. Thus, higher doses of caffeine can cause an increase in A(1) agonist binding without a corresponding change in A(1) mRNA or in A(1) antagonist binding, suggesting that the adaptive changes seen upon prolonged caffeine treatment may be in sites different from A(1) receptors. Caffeine (1 g/l) increased A(2A) receptors in the striatum measured as binding of the agonist [H-3]CGS 21680 suggesting that up-regulation of A(2A) receptors may be an adaptive effect of caffeine intake. (C) 1997 Elsevier Science B.V.