Pharmacological characterization of A2-adenosine receptors in guinea-pig ventricular cardiomyocytes.
Pharmacological characterization of A2-adenosine receptors in guinea-pig ventricular cardiomyocytes.
复制标题
豚鼠心室心肌细胞 A2-腺苷受体的药理学特征。
DOI：
10.1006/jmcc.1994.1049
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发表时间：
1994
影响因子：
5
通讯作者：
C. Seeland
中科院分区：
文献类型：
--
作者：
B. Stein;W. Schmitz;H. Scholz;C. Seeland
本研究的目的是阐明心肌细胞是否具有刺激性腺苷酸环化酶偶联A2-腺苷受体，以及这些受体是否改变收缩性的问题。在离体电驱动的豚鼠心室肌细胞中，研究了A2-腺苷受体激动剂2-[（p-2-羧乙基）-苯乙氨基]-5 '-N-乙基甲酰胺-腺苷（CGS 21680 C）单独和在异丙肾上腺素存在下对cAMP含量和收缩反应的影响。此外，我们用选择性A1-和A2-腺苷受体拮抗剂[分别为1，3-二丙基-8-环戊基黄嘌呤，DPCPX和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，CGS 15943 A]表征了这些作用。为了研究信号转导途径，研究了已知抑制信号转导GTP结合蛋白（Gi/o-蛋白）的百日咳毒素对这些效应的影响。CGS 21680 C单独和在异丙肾上腺素的存在下增加cAMP含量浓度依赖性（0.1 nmol/l-10 mumol/l），最大值分别为对照组的154%和异丙肾上腺素值的137%。在A1-腺苷受体拮抗剂DPCPX（0.3 μ mol/l）存在下或百日咳毒素预处理（18 μ g/kg i. v. 24-26 h）后，cAMP增加进一步升高。A2-腺苷受体拮抗剂CGS 15943 A（0.01 μ mol/l）消除了这些作用，表明这些作用是由A2-腺苷受体介导的。cAMP含量的升高并不伴随着收缩反应的增加。然而，在异丙肾上腺素的存在下，CGS 21680 C将收缩反应降低至异丙肾上腺素值的62%。A1-腺苷受体拮抗剂DPCPX消除了收缩力的下降，而A2-腺苷受体拮抗剂CGS 15943 A没有影响收缩力。因此，收缩力的降低是通过cAMP减少A1-腺苷受体介导的。结果为心室肌细胞上cAMP降低型A1-腺苷受体和cAMP升高型A2-腺苷受体的共存提供了证据。只有A1-腺苷受体的刺激导致随后的收缩反应的减少，而A2-腺苷受体不影响收缩性。
The aim of the present study was to elucidate the question of whether cardiomyocytes possess stimulatory adenylyl cyclase-coupled A2-adenosine receptors and whether these receptors modify contractility. In isolated electrically driven ventricular cardiomyocytes from guinea-pig hearts the effects of the A2-adenosine receptor agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamide-adenos ine (CGS 21680C) alone and in the presence of isoprenaline on cAMP content and contractile response were investigated. In addition, we characterized these effects with selective A1- and A2-adenosine receptor antagonists [1,3-dipropyl-8-cyclopentylxanthine, DPCPX and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo-(1,5-c)quinazolin++ +-5-imine, CGS 15943A, respectively]. To investigate the signal transduction pathway, the influence of pertussis toxin, known to inhibit signal transducing GTP-binding proteins (Gi/o-proteins), on these effects was studied. CGS 21680C alone and in the presence of isoprenaline increased cAMP content concentration-dependently (0.1 nmol/l-10 mumol/l) to maximally 154% of control and 137% of isoprenaline value, respectively. In the presence of the A1-adenosine receptor antagonist DPCPX (0.3 mumol/l) or after pertussis toxin-pretreatment (18 micrograms/kg i.v. 24-26 h) the cAMP increase was further elevated. The A2-adenosine receptor antagonist CGS 15943A (0.01 mumol/l) abolished these effects, indicating that these effects are mediated by A2-adenosine receptors. The elevation in cAMP content was not accompanied by an increase in contractile response. However, in the presence of isoprenaline CGS 21680C reduced contractile response to 62% of the isoprenaline value. The A1-adenosine receptor antagonist DPCPX abolished the decrease in contractility, whereas the A2-adenosine receptor antagonist CGS 15943A did not effect contractility. Thus the reduction in contractility is mediated via cAMP-decreasing A1-adenosine receptors. The results provide evidence for the coexistence of cAMP-reducing A1- and cAMP-elevating A2-adenosine receptors on ventricular cardiomyocytes. Only stimulation of A1-adenosine receptors leads to a subsequent reduction in contractile response, whereas A2-adenosine receptors do not affect contractility.