BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS IN SHEEP CARDIAC VENTRICULAR MUSCLE
BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS IN SHEEP CARDIAC VENTRICULAR MUSCLE
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DOI：
10.1016/0022-2828(92)93389-2
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发表时间：
1992-07-01
影响因子：
5
通讯作者：
MUGELLI, A
中科院分区：
文献类型：
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作者：
BOREA, PA;AMERINI, S;MUGELLI, A
用放射性配体结合技术和功能研究方法，对绵羊心室肌β2肾上腺素能受体的存在进行了研究。在膜制备物中，[3 H]-二氢阿普洛尔与选择性β1-拮抗剂CGP 20712 A（0.1 nm-1 mm）之间的竞争曲线明显呈双相，并显示存在两个不同的结合位点，对CGP 20712 A的亲和力（pKD）分别为9.5 ± 0.9和4.5 ± 0.4。左、右心室β1：β 2受体的相对比例约为70：30。在以1Hz驱动的心室小梁中，异丙肾上腺素（1-300 nm）引起收缩力的剂量依赖性增加，最大效应为298 ± 26 mg，与达到峰值张力的时间（t1，斜向效应）和松弛时间（t2，斜向效应）的减少有关。用0.1 μmCGP 20712 A或选择性β2受体拮抗剂ICI 118 551（50 nm）预处理，异丙肾上腺素的正性肌力量效曲线明显右移。在CGP 20712 A（0.1 μm）存在下，浓度高达10 μm的异丙肾上腺素对两者均无影响;另一方面，用ICI 118 551（50 nm）预处理制剂可完全拮抗异丙肾上腺素的变向性效应，但不拮抗其向异性效应。在CGP 20712 A丙卡特罗（0.01-10 μm）（一种β2-肾上腺素受体激动剂）存在下，诱导正性内向效应，但与任何显著修饰无关。ICI 118 551（50 nm）完全消除了该效应。异丙肾上腺素（1 μm）的正性肌力作用与在−60 mV下测量的动作电位时程显著缩短相关（在不存在和存在异丙肾上腺素的情况下分别为220 ± 8和193 ± 10 ms;P<0.05）。在单独存在CGP 20712 A（0.1 μm）的情况下，异丙肾上腺素（1μm）仍诱导收缩力显著增加，但动作电位曲线仅受到轻微影响。CGP 20712 A和ICI 118 551（10 nm）的同时存在可完全拮抗异丙肾上腺素的作用。结果表明，绵羊心室肌中β_1和β_2肾上腺素能受体共存，它们的兴奋可介导正性变力作用。然而，它们在抽搐的松弛阶段的功能作用可能是不同的。
The presence ofβ2-adrenoceptors in the sheep ventricular myocardium was assessed by the radioligand binding technique and functional studies. In membrane preparations, the competition curve between [3H]-dihydroalprenolol and the selectiveβ1-antagonist CGP 20712A (0.1 nm–1 mm) was clearly biphasic, and revealed the presence of two different binding sites showing an affinity (pKD) for CGP 20712A of 9.5 ± 0.9 and 4.5 ± 0.4, respectively. The relative proportion ofβ1:β2adrenoceptors was about 70:30 in both the right and left ventricle. In ventricular trabeculae driven at 1Hz, isoprenaline (1–300 nm) caused a dose-dependent increase in the force of contraction, the maximum effect being 298 ± 26 mg, associated with reduction of time to peak tension (t1, clinotropic effect) and relaxation time (t2, lusitropic effect). The inotropic dose-response curve for isoprenaline was significantly shifted to the right by pretreatment of the preparations with 0.1 μmCGP 20712A or with the selectiveβ2-antagonist ICI 118 551 (50 nm). In the presence of CGP 20712A (0.1 μm), isoprenaline, up to a concentration of 10 μm, did not affect eithert1ort2; on the other hand, pretreatment of the preparations with ICI 118 551 (50 nm) fully antagonized the clinotropic but not the lusitropic effect of isoprenaline. In the presence of CGP 20712A procaterol (0.01–10 μm), aβ2-adrenoceptor agonist, induced a positive intropic effect which was not associated with any significant modifications int1ort2. This effect was completely abolished by ICI 118 551 (50 nm).The positive inotropic action of isoprenaline (1 μm) was associated with a significant decrease in action potential duration measured at −60 mV (220 ± 8 and 193 ± 10 ms in the absence and presence of isoprenaline, respectively;P<0.05). In the presence of CGP 20712A (0.1 μm) alone, isoprenaline (1μm) still induced a significant increase in contractility but the action potential profile was only slightly affected. The effects of isoprenaline were fully antagonized by the simultaneous presence of CGP 20712A and ICI 118 551 (10 nm). It is concluded that bothβ1- andβ2-adrenoceptors appear to coexist in sheep ventricular myocardium where their stimulation mediates a positive inotropic effect. However, their functional role on the relaxation phase of the twitch may be different.