BETA-ADRENERGIC RECEPTORS AND CYCLIC ADENOSINE-MONOPHOSPHATE GENERATION IN HUMAN-FETAL LUNG
BETA-ADRENERGIC RECEPTORS AND CYCLIC ADENOSINE-MONOPHOSPHATE GENERATION IN HUMAN-FETAL LUNG
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DOI：
10.1203/00006450-198702000-00007
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发表时间：
1987-02-01
影响因子：
3.6
通讯作者：
ROBERTS, JM
中科院分区：
文献类型：
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作者：
DAVIS, DJ;DATTEL, BJ;ROBERTS, JM
我们设计了实验来确定β-肾上腺素能受体存在于妊娠晚期的人胎儿肺中并发挥功能。为了确定β的存在，受体，表征它们的结合位点，并评估受体随胎龄的变化，我们用特异性的、高亲和力的β-受体进行了放射性配体结合测定。拮抗剂，125 I-碘氰基吲哚酚，在膜颗粒从第2个三月流产（15-23周）。125 I-碘氰基吲哚酚的结合是可饱和的，并且具有高亲和力（解离常数= 40 pM）。通过普萘洛尔的（-）和（+）立体异构体的竞争研究确定结合具有立体选择性。激动剂亲和力（异丙肾上腺素>肾上腺素. mchgt.去甲肾上腺素）与β-肾上腺素的优势一致。2受体的竞争研究证实了这种优势，β 2受体拮抗剂ICI 118-551（75% β- 2.25% β- 1）。β的浓度-肾上腺素能受体随胎龄增加而增加。为了评估β的功能偶联，受体，我们测试了受体占用激活腺苷酸环化酶的能力。对于该测定，我们将切碎的人胎肺与β-雌二醇孵育。激动剂并测定产生的cAMP的量。β。激动剂刺激cAMP生成超过2倍。我们得出结论，β-肾上腺素能受体早在妊娠中期就存在于人胎儿肺中并起作用。
We designed experiments to determine whether .beta.-adrenaergic receptors are present and functional in human fetal lung during te 2nd trimester of gestation. To determine the presence of .beta. receptors, characterize their binding sites, and assess changes in receptor with gestational age, we performed radioligand binding assays with the specific, high-affinity .beta. antagonist, 125I-iodocyanopindolol, in membrane particulates from the lungs of 2nd trimester abortuses (15-23 wk). Binding of 125I-iodocyanopindolol was saturable and of high affinity (dissociation constant = 40 pM). Binding was stereoselective as determined by competition studies with (-) and (+) stereoisomers of propranolol. Agonist affinities (isoproterenol > epinephrine .mchgt. norephinephrine) were consistent with a predominance of .beta.-2 receptors; this predominance was confirmed by competition studies with the specific .beta.-2 receptor antagonist ICI 118-551 (75% .beta.-2, 25% .beta.-1). The concentration of .beta.-adrenergic receptors increased with gestational age. To assess the functional coupling of the .beta. receptors, we tested the ability of receptor occupancy to activate adenylate cyclase. For this assay, we incubated minced human fetal lung with .beta. agonists and determined the amount of cAMP generated. .beta. Agonists stimulated cAMP generation more than 2-fold. We conclude that .beta.-adrenergic receptors are present and functional in human fetal lung as early as the 2nd trimester.