Adenosine receptor-mediated inhibition of cardiac adenylyl cyclase activity may involve multiple receptor subtypes.
Adenosine receptor-mediated inhibition of cardiac adenylyl cyclase activity may involve multiple receptor subtypes.
复制标题
腺苷受体介导的心脏腺苷酸环化酶活性抑制可能涉及多种受体亚型。
DOI：
10.1007/bf00178210
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Green,RD
中科院分区：
文献类型：
--
作者：
Ma,H;Yu,HJ;Green,RD
我们之前报道过，在肾上腺素受体激动剂异丙肾上腺素存在的情况下，腺苷受体激动剂 N6-苯基异丙基腺苷 (R-PIA) 会抑制去污剂透化的胚胎鸡心室肌细胞中的腺苷酸环化酶 (Ma 和 Green 1992)。这种抑制作用的剂量反应曲线的斜率非常浅（nH0.3-0.4）。目前对去污剂透化的鸡肌细胞的研究评估了这种浅抑制曲线的机制。我们发现，与 R-PIA 相比，另外两种腺苷受体激动剂 N6-环戊基腺苷 (CPA) 和 2-氯-N6-环戊基腺苷 (CCPA) 以单相、剂量依赖性方式抑制心脏腺苷酸环化酶活性 (nH∼1)。两种 A1 腺苷受体拮抗剂 8-环戊基-1,3,-二丙基黄嘌呤 (CPX) 和 3-(4-氨基)苯乙基-1-丙基-8-环戊基黄嘌呤 (BW A884U) 对 R-PIA 反应的影响不同。 BW A884U 以平行方式将 R-PIA 剂量反应曲线向右移动，而 CPX 既移动 R-PIA 反应曲线又增加其陡度。使用一种拮抗剂 ([3H]CPX) 和两种激动剂 ([3H]R-PIA 和 [3H]CCPA) 放射性配体进一步表征心脏 A1 腺苷受体。 [3H]CPX 与去污剂透化的心室肌细胞中的腺苷受体结合，Kd 值为 3.3±0.2 nM，BMAX 值为 30.1 ± 2.4 fmol/mg 蛋白质（平均值 ± SEM；N= 4）。 [3H]R-PIA 比 [3H]CCPA 检测到更多位点（分别为 22.8 ±4.0 和 8.3 ± 1.3 fmol/mg 蛋白质；无 GTP 条件）。 CPA和CCPA以浅的、剂量依赖的方式抑制[3H]R-PIA结合(nH∼0.4)，而R-PIA和CPA抑制[3H]CCPA与nH∼1的结合。这些结果表明存在不止一种腺苷受体亚型，并且可以与胚胎鸡心肌细胞中腺苷酸环化酶的抑制相耦合。
We previously reported that the adenosine receptor agonist N6-phenylisopropyladenosine (R-PIA) inhibits adenylyl cyclase in detergent-permeabilized embryonic chick ventricular myocytes in the presence of the adrenergic receptor agonist, isoproterenol (Ma and Green 1992). The slope of the dose response curve of this inhibition is very shallow (nH0.3–0.4). The present studies on detergent-permeabilized chick myocytes evaluate the mechanisms underlying this shallow inhibition curve. We find that in contrast to R-PIA, two additional adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and 2-chloro-N6-cyclopentyladenosine (CCPA), inhibit cardiac adenylyl cyclase activity in a monophasic, dose-dependent manner (nH∼1). Two A1adenosine receptor antagonists, 8-cyclopentyl-1,3,-dipropylxanthine (CPX) and 3-(4-amino)phenethyl-l-propyl-8-cyclopentylxanthine (BW A884U) affect the R-PIA responses differently. BW A884U shifts the R-PIA dose response curve to the right in a parallel fashion while CPX both shifts the R-PIA response curve and increases its steepness. Cardiac A1adenosine receptors were further characterized using one antagonist ([3H]CPX) and two agonist ([3H]R-PIA and [3H]CCPA) radioligands. [3H]CPX binds to the adenosine receptors in detergent-permeabilized ventricular myocytes with a Kdvalue of 3.3±0.2 nM and a BMAXvalue of 30.1 ± 2.4 fmol/mg protein (means ± SEM;N= 4). [3H]R-PIA detects more sites than [3H]CCPA (22.8 ±4.0 and 8.3 ± 1.3 fmol/mg protein, respectively; GTP-free conditions). CPA and CCPA inhibit [3H]R-PIA binding in a shallow, dose-dependent manner (nH ∼ 0.4), while R-PIA and CPA inhibit [3H]CCPA binding with a nH∼1. These results suggest that more than one subtype of adenosine receptor is present and can couple to the inhibition of adenylyl cyclase in embryonic chick cardiac myocytes.