Adenosine receptor coupling to adenylate cyclase of rat ventricular myocyte membranes.
Adenosine receptor coupling to adenylate cyclase of rat ventricular myocyte membranes.
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DOI：
10.1152/ajpheart.1989.257.4.h1088
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发表时间：
1989-10
期刊：
影响因子：
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通讯作者：
Fred D. Romano;Susan G. MacDonald;J. Dobson
中科院分区：
文献类型：
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作者：
Fred D. Romano;Susan G. MacDonald;J. Dobson
腺苷类似物对β-肾上腺素能受体的影响和受体非依赖性引起的腺苷酸环化酶活性的增加进行了研究，使用从成年大鼠心室肌细胞的原代培养物获得的膜。苯异丙基腺苷，A1受体激动剂，在0.1，1.0和10 μ M的浓度，最大限度地抑制异丙肾上腺素刺激的腺苷酸环化酶活性的35，55和41%，分别。10 μ M茶碱可拮抗苯异丙基腺苷的抑制作用。1微摩尔苯基异丙基腺苷在减弱毛喉素刺激活性方面的效果要差得多，因此最大抑制率为26%。苯基异丙基腺苷对5 '-鸟苷酰亚胺二磷酸对腺苷酸环化酶的刺激没有影响。Phenylaminoadenosine，一种A2激动剂，在10 μ M或更高浓度下刺激腺苷酸环化酶活性。茶碱或0.1 μ M的1，3-二丙基-8-环戊基黄嘌呤（DPCPX），拮抗苯异丙基腺苷抑制异丙肾上腺素刺激的腺苷酸环化酶活性，这种作用没有显着抑制。此外，N-乙基甲酰氨基腺苷，一种非选择性腺苷受体激动剂，在没有DPCPX的情况下对腺苷酸环化酶活性没有影响，但在DPCPX存在下刺激腺苷酸环化酶活性。上述结果表明，A1和A2受体均存在于心室肌细胞膜上。更重要的是，研究结果表明，腺苷抑制儿茶酚胺刺激的腺苷酸环化酶活性主要是由于β-肾上腺素能受体介导的转导的改变，并可能部分由催化成分的直接抑制。
The effects of adenosine analogues on beta-adrenergic receptor and receptor-independent elicited increases in adenylate cyclase activity were investigated using membranes obtained from primary cultures of adult rat ventricular myocytes. Phenylisopropyladenosine, an A1-receptor agonist, at concentrations of 0.1, 1.0, and 10 microM, maximally inhibited isoproterenol-stimulated adenylate cyclase activity by 35, 55, and 41%, respectively. The inhibition by phenylisopropyladenosine was antagonized by 10 microM theophylline. One micromolar phenylisopropyladenosine was much less effective at attenuating forskolin-stimulated activity, such that the maximum inhibition was 26%. Phenylisopropyladenosine had no effect on adenylate cyclase stimulation by 5'-guanylylimidodiphosphate. Phenylaminoadenosine, an A2 agonist, at 10 microM or greater stimulated adenylate cyclase activity. This effect was not significantly inhibited by theophylline or 0.1 microM 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), which antagonized phenylisopropyladenosine inhibition of isoproterenol-stimulated adenylate cyclase activity. Additionally, N-ethylcarboxamidoadenosine, a nonselective adenosine-receptor agonist, had no effect on adenylate cyclase activity in the absence of DPCPX but stimulated adenylate cyclase activity in the presence of DPCPX. These results indicate that both A1 and A2 receptors exist on the ventricular myocyte sarcolemma. More importantly, the findings suggest that adenosine inhibition of catecholamine-stimulated adenylate cyclase activity is primarily due to an alteration in beta-adrenergic receptor-mediated transduction and perhaps in part by a direct inhibition of the catalytic component.