Schiele J O, Schwabe U
Pharmakologisches Institut, Universität Heidelberg, Germany.
Eur J Pharmacol. 1994 Sep 15;269(1):51-8. doi: 10.1016/0922-4106(94)90025-6.
In the present work we studied the effect of adenosine and various adenosine analogues on cAMP level in guinea pig coronary endothelial cells of microvascular origin. The tested adenosine agonist mediate a concentration-dependent increase in cAMP level. The rank order of potency was 5'-N-ethylcarboxamidoadenosine (NECA) > CGS 21680 > N6-phenylisopropyladenosine (R-PIA) > 2-chloro-N6-cyclopentyladenosine (CCPA) which is typical for an adenosine A2 receptor. Their respective concentrations for half maximal stimulation of cAMP formation were 0.36 microM, 0.82 microM, 4.7 microM and 9.8 microM. The tested agonists showed differences in efficacy, NECA being the most efficacious. R-PIA, CCPA and adenosine were less efficacious, suggesting partial agonism. The efficacy of adenosine was unchanged by the addition of the nucleoside transport inhibitor S(4-nitrobenzyl)-6-thioinosine (NBTI, 10 microM) suggesting that inhibition of adenylyl cyclase through P-site activation is not responsible for the observed low efficacy of adenosine. We could demonstrate CGS 21680 activation of adenylyl cyclase in a peripheral receptor. We therefore suggest that the endothelial adenosine receptor resembles the striatal adenosine A2a receptor.
在本研究中，我们研究了腺苷及多种腺苷类似物对微血管来源的豚鼠冠状动脉内皮细胞中环磷酸腺苷（cAMP）水平的影响。所测试的腺苷激动剂介导了cAMP水平的浓度依赖性升高。效力顺序为5'-N-乙基羧酰胺腺苷（NECA）> CGS 21680 > N6-苯基异丙基腺苷（R-PIA）> 2-氯-N6-环戊基腺苷（CCPA），这是腺苷A2受体的典型特征。它们各自使cAMP形成达到半数最大刺激的浓度分别为0.36微摩尔/升、0.82微摩尔/升、4.7微摩尔/升和9.8微摩尔/升。所测试的激动剂在效力上存在差异，NECA效力最强。R-PIA、CCPA和腺苷的效力较低，提示存在部分激动作用。添加核苷转运抑制剂S(4-硝基苄基)-6-硫代肌苷（NBTI，10微摩尔/升）后，腺苷的效力未发生改变，这表明通过P位点激活抑制腺苷酸环化酶并非腺苷效力低的原因。我们能够证明CGS 21680可激活外周受体中的腺苷酸环化酶。因此，我们认为内皮腺苷受体类似于纹状体腺苷A2a受体。
