Preston Z, Lee K, Widdowson L, Freeman T C, Dixon A K, Richardson P J
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ.
Br J Pharmacol. 2000 Jun;130(4):886-90. doi: 10.1038/sj.bjp.0703366.
Cholinergic neurons were identified in rat striatal slices by their size, membrane properties, sensitivity to the NK(1) receptor agonist (Sar(9), Met(O(2))(11)) Substance P, and expression of choline acetyltransferase mRNA. A(1) receptor mRNA was detected in 60% of the neurons analysed, and A(2A) receptor mRNA in 67% (n=15). The A(1) receptor agonist R-N(6)-(2-phenylisopropyl)adenosine (R-PIA) hyperpolarized cholinergic neurons in a concentration dependent manner sensitive to the A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 100 nM). In dual stimulus experiments, the A(2A) receptor antagonist 8-(3-chlorostyryl)caffeine (CSC, 500 nM) decreased release of [(3)H]-acetylcholine from striatal slices (S2/S1 0.78+/-0.07 versus 0.95+/-0.05 in control), as did adenosine deaminase (S2/S1 ratio 0.69+/-0.05), whereas the A(1) receptor antagonist DPCPX (100 nM) had no effect (S2/S1 1.05+/-0.14). In the presence of adenosine deaminase the adenosine A(2A) receptor agonist 2-p-((carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamidoadeno sin e (CGS21680, 10 nM) increased release (S2/S1 ratio 1.03+/-0.05 versus 0.88+/-0.05 in control), an effect blocked by the antagonist CSC (500 nM, S2/S1 0.68+/-0.05, versus 0.73+/-0.08 with CSC alone). The combined superfusion of bicuculline (10 microM), saclofen (1 microM) and naloxone (10 microM) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99+/-0.04). The A(1) receptor agonist R-PIA (100 nM) inhibited the release of [(3)H]-acetylcholine (S2/S1 ratio 0.70+/-0.03), an effect blocked by DPCPX (S2/S1 ratio 1.06+/-0.07). It is concluded that both A(1) and A(2A) receptors are expressed on striatal cholinergic neurons where they are functionally active.
通过大鼠纹状体切片中胆碱能神经元的大小、膜特性、对NK(1)受体激动剂（Sar(9)，Met(O(2))(11)）P物质的敏感性以及胆碱乙酰转移酶mRNA的表达来鉴定胆碱能神经元。在所分析的神经元中，60%检测到A(1)受体mRNA，67%检测到A(2A)受体mRNA（n = 15）。A(1)受体激动剂R-N(6)-(2-苯异丙基)腺苷（R-PIA）以浓度依赖性方式使胆碱能神经元超极化，该作用对A(1)拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX，100 nM）敏感。在双刺激实验中，A(2A)受体拮抗剂8-(3-氯苯乙烯基)咖啡因（CSC，500 nM）降低了纹状体切片中[(3)H]-乙酰胆碱的释放（S2/S1为0.78±0.07，而对照组为0.95±0.05），腺苷脱氨酶也有同样作用（S2/S1比值为0.69±0.05），而A(1)受体拮抗剂DPCPX（100 nM）则无作用（S2/S1为1.05±0.14）。在存在腺苷脱氨酶的情况下，腺苷A(2A)受体激动剂2-p-((羧乙基)苯乙氨基)-5'-N-乙基羧酰胺腺苷（CGS21680，10 nM）增加了释放（S2/S1比值为1.03±0.05，而对照组为0.88±0.05），该作用被拮抗剂CSC（500 nM）阻断（S2/S1为0.68±0.05，与单独使用CSC时的0.73±0.08相比）。荷包牡丹碱（10 microM）、氯苯氨丁酸（1 microM）和纳洛酮（10 microM）联合灌流对CGS21680的刺激无影响（S2/S1比值为0.99±0.04）。A(1)受体激动剂R-PIA（100 nM）抑制了[(3)H]-乙酰胆碱的释放（S2/S1比值为0.70±0.03），该作用被DPCPX阻断（S2/S1比值为1.06±0.07）。结论是，A(1)和A(2A)受体均在纹状体胆碱能神经元上表达，且在这些神经元上具有功能活性。
