Felsch A, Stöcker K, Borchard U
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Eur J Pharmacol. 1994 Oct 3;263(3):261-8. doi: 10.1016/0014-2999(94)90721-8.
The actions of the adenosine A1 receptor agonist CCPA (2-chloro-N6-cyclopentyladenosine) and the adenosine A2 receptor agonist CGS 21680 (2-[p-(2-carboxyethyl(phenethylamino]-5'-N- ethylcarboxamidoadenosine) on myocardial functions and prostacyclin release were studied in Langendorff-perfused guinea-pig hearts. In spontaneously beating hearts, perfused at constant pressure, CCPA reduced heart rate and left ventricular actively developed pressure with EC50 values of 54.4 +/- 8.7 nM and 81 +/- 6.2 nM, respectively. The adenosine A1 receptor antagonist PACPX (1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine, 1 microM) antagonized the effects of CCPA on heart rate and left ventricular actively developed pressure and increased the EC50 values 11-fold and 8-fold, respectively. CGS 21680 caused vasodilatation and doubled the coronary flow rate (EC50 of 5.77 +/- 3 nM). The potent but non-selective adenosine receptor antagonist CGS 15943A (9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin++ +-5-imine, 0.1 microM) caused a shift to the right of the concentration-response curve of CGS 21680 for coronary flow rate and increased the EC50 value 52-fold. In electrically paced hearts, perfused at constant flow rate, CCPA (1-100 nM) and CGS 21680 (10-1000 nM) increased the 6-oxo-prostaglandin F1 alpha release (stable non-enzymatic hydrolysis product of prostacyclin) into the cardiac effluent to a maximum of 170 +/- 16% and 184 +/- 6%, respectively. The effects of CCPA and CGS 21680 on cardiac functions indicate a high selectivity of both agonists for adenosine A1 and A2 receptor subtypes of the isolated guinea-pig heart, respectively. The elevation of 6-oxo-prostaglandin F1 alpha in the effluent of guinea-pig hearts by CCPA and CGS 21680 is possibly independent of stimulation of adenosine receptors on the vascular endothelium.
在Langendorff灌注的豚鼠心脏中，研究了腺苷A1受体激动剂CCPA（2-氯-N6-环戊基腺苷）和腺苷A2受体激动剂CGS 21680（2-[对-(2-羧乙基苯乙氨基)]-5'-N-乙基羧酰胺腺苷）对心肌功能和前列环素释放的作用。在恒压灌注的自主搏动心脏中，CCPA降低心率和左心室主动收缩压，其半数有效浓度（EC50）值分别为54.4±8.7 nM和81±6.2 nM。腺苷A1受体拮抗剂PACPX（1,3-二丙基-8-(2-氨基-4-氯)苯基黄嘌呤，1 μM）拮抗CCPA对心率和左心室主动收缩压的作用，并分别使EC50值增加11倍和8倍。CGS 21680引起血管舒张，并使冠状动脉血流量增加一倍（EC50为5.77±3 nM）。强效但非选择性的腺苷受体拮抗剂CGS 15943A（9-氯-2-(2-呋喃基)-5,6-二氢-1,2,4-三唑并(1,5-c)喹唑啉-5-亚胺，0.1 μM）使CGS 21680冠状动脉血流量浓度-反应曲线右移，并使EC50值增加52倍。在恒流灌注的电起搏心脏中，CCPA（1-100 nM）和CGS 21680（10-1000 nM）使心脏流出液中6-氧代前列腺素F1α（前列环素的稳定非酶水解产物）的释放分别增加至最大值的170±16%和184±6%。CCPA和CGS 21680对心脏功能的作用表明，这两种激动剂分别对离体豚鼠心脏的腺苷A1和A2受体亚型具有高度选择性。CCPA和CGS 21680使豚鼠心脏流出液中6-氧代前列腺素F1α升高，这可能与刺激血管内皮上的腺苷受体无关。
