COEXISTENCE OF BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS IN HUMAN RIGHT ATRIUM - DIRECT IDENTIFICATION BY (+/-)-[I-125]IODOCYANOPINDOLOL BINDING
COEXISTENCE OF BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS IN HUMAN RIGHT ATRIUM - DIRECT IDENTIFICATION BY (+/-)-[I-125]IODOCYANOPINDOLOL BINDING
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DOI：
10.1161/01.res.53.6.752
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发表时间：
1983-01-01
影响因子：
20.1
通讯作者：
REIDEMEISTER, JC
中科院分区：
文献类型：
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作者：
BRODDE, OE;KARAD, K;REIDEMEISTER, JC
高度特异性的β-肾上腺素受体放射性配体，（±）- [125 I]碘氰基吲哚酚用于将β-心脏直视手术中获得的人右心耳膜中的肾上腺素受体。（.+-.）-的约束力[125 I]碘氰基吲哚酚是可饱和的（Bmax = 86.4 ± 0.001）。7.4 fmol（.+-.）- [125 I]碘氰基吲哚酚结合/mg蛋白质，n = 4），具有高亲和力（Kd = 53 ± 0.01）。6 pM，n = 4），快速，可逆和立体特异性。异丙肾上腺素、肾上腺素和去甲肾上腺素抑制（. ±.）- [125 I]碘氰基吲哚酚结合和腺苷酸环化酶的活化为1：10：10，表明主要由β 1-肾上腺素受体组成的群体。抑制（.+-.）-然而，β 1-（普萘洛尔、美托洛尔、倍他洛尔）和β 2-（IPS 339、ICI 118，551、锌特罗、丙卡特罗）选择性药物与[125 I]碘氰基吲哚洛尔的结合导致双相位移曲线，斜率因子（nH，假希尔系数）显著< 1.0。这些曲线的非线性回归分析揭示了人右心房附件中β 1：β 2的比例为80：20。非选择性β-肾上腺素能药物（普萘洛尔，异丙肾上腺素和肾上腺素），相反，抑制结合的双相位移曲线和nH = 1.0。激动剂与β-受体的结合人右心耳的肾上腺素能受体似乎受鸟苷酸的调节。在没有GTP的情况下，异丙肾上腺素结合高和低亲和力状态的β-肾上腺素受体GTP（10-4 M）将这种异质结合转化为低亲和力的同质结合。显然，在人的右心房中，β 1-和β 2-肾上腺素受体共存;然而，β 1-肾上腺素受体占优势。人右心房中β 2-肾上腺素受体的生理功能仍有待阐明。
The highly specific .beta.-adrenoceptor radioligand, (.+-.)-[125I]iodocyanopindolol, was used to subclassify .beta.-adrenoceptors in membranes from human right atrial appendage obtained during open heart surgery. Binding of (.+-.)-[125I]iodocyanopindolol was saturable (Bmax = 86.4 .+-. 7.4 fmol (.+-.)-[125I]iodocyanopindolol bound/mg protein, n = 4), of high affinity (Kd = 53 .+-. 6 pM, n = 4), rapid, reversible and stereospecific. The relative potencies of isoprenaline, adrenaline [epinephrine], and noradrenaline [norepinephrine] for inhibition of (.+-.)-[125I]iodocyanopindolol binding and activation of adenylate cyclase were 1:10:10, indicating a population composed mainly of .beta.1-adrenoceptors. Inhibition of (.+-.)-[125I]iodocyanopindolol binding by .beta.1- (practolol, metoprolol, betaxolol) and .beta.2- (IPS 339, ICI 118,551, zinterol, procaterol) selective drugs, however, resulted in biphasic displacement curves with slope factors (nH, pseudo Hill coefficients) significantly < 1.0. Nonlinear regression analysis of these curves revealed a .beta.1:.beta.2 ratio of 80:20 in human right atrial appendage. Nonselective .beta.-adrenergic drugs (propranolol, isoprenaline and adrenaline), on the contrary, inhibited binding with monophasic displacement curves and nH = 1.0. Binding of agonists to the .beta.-adrenoceptors in human right atrial appendage seems to be regulated by guanyl nucleotides. In the absence of GTP, isoprenaline binds to high and low affinity state of the .beta.-adrenoceptors. GTP (10-4 M) converts this heterogeneous binding into a homogeneous one of low affinity. Evidently, in human right atria, .beta.1- and .beta.2-adrenoceptors coexist; however, .beta.1-adrenoceptors predominate. The physiological function of .beta.2-adrenoceptors in human right atrium remains to be elucidated.