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牛垂体滤泡星状细胞具有与3',5'-环磷酸腺苷生成正偶联的β-肾上腺素能受体。

Bovine pituitary folliculo-stellate cells have beta-adrenergic receptors positively coupled to adenosine 3',5'-cyclic monophosphate production.

作者信息

Findell P R, Weiner R I

机构信息

Reproductive Endocrinology Center, University of California, San Francisco 94143.

出版信息

Endocrinology. 1988 Nov;123(5):2454-61. doi: 10.1210/endo-123-5-2454.

Abstract

The specific beta-adrenergic radioligand [125I]iodocyanopindolol (ICYP) was used to identify and characterize beta-adrenergic receptors in bovine pituitary folliculo-stellate cells (bFSC) grown in culture. Saturation analysis demonstrated the binding of ICYP to bFSC particulate fractions to be of high affinity (apparent Kd = 80 pM) and low capacity (Bmax = 37 fmol/mg protein). The specific beta-adrenergic radioligand [3H] dihydroalprenolol also bound to bFSC particulate preparations with parameters compatible with binding to the beta-adrenergic receptor (Kd = 3.0 nM; Bmax = 52 fmol/mg protein). No specific binding was observed with either the dopamine receptor radioligand [3H]spiperone or the alpha-adrenergic radioligand [3H]dihydro-alpha-ergocryptine. The bFSC beta-adrenergic receptors were further characterized by computer modeling of competition studies with a variety of agonists and antagonists selective for beta-adrenergic subtypes. The pharmacological profiles of ICYP binding obtained from these studies indicated that approximately equal proportions of both beta 1- and beta 2-adrenergic subtypes are expressed in cultured bFSC. Bovine FSC beta-adrenergic receptors are functionally coupled to activation of cAMP. The beta-adrenergic agonists isoproterenol, epinephrine, and norepinephrine provoked a rapid and marked stimulation of intracellular cAMP accumulation. The approximately equipotent effect of epinephrine and norepinephrine indicated that the beta-adrenergic effect on cAMP production is principally mediated via the beta 1-adrenergic receptor. The identification of beta-adrenergic receptors on bFSC positively coupled to adenylate cyclase provides a possible regulatory control pathway for the proposed role of pituitary FSC in the modulation of anterior pituitary hormone secretion.

摘要

特异性β-肾上腺素能放射性配体[125I]碘氰吲哚洛尔(ICYP)用于鉴定和表征培养的牛垂体滤泡星状细胞(bFSC)中的β-肾上腺素能受体。饱和分析表明,ICYP与bFSC微粒部分的结合具有高亲和力(表观Kd = 80 pM)和低容量(Bmax = 37 fmol/mg蛋白)。特异性β-肾上腺素能放射性配体[3H]二氢阿普洛尔也与bFSC微粒制剂结合,其参数与β-肾上腺素能受体结合相符(Kd = 3.0 nM;Bmax = 52 fmol/mg蛋白)。多巴胺受体放射性配体[3H]螺哌隆或α-肾上腺素能放射性配体[3H]二氢-α-麦角隐亭均未观察到特异性结合。通过对与多种β-肾上腺素能亚型选择性激动剂和拮抗剂的竞争研究进行计算机建模,进一步表征了bFSCβ-肾上腺素能受体。这些研究获得的ICYP结合的药理学特征表明,培养的bFSC中β1-和β2-肾上腺素能亚型的表达比例大致相等。牛FSCβ-肾上腺素能受体在功能上与cAMP的激活偶联。β-肾上腺素能激动剂异丙肾上腺素、肾上腺素和去甲肾上腺素可迅速且显著地刺激细胞内cAMP积累。肾上腺素和去甲肾上腺素的等效效应表明,β-肾上腺素能对cAMP产生的作用主要通过β1-肾上腺素能受体介导。bFSC上与腺苷酸环化酶正偶联的β-肾上腺素能受体的鉴定为垂体FSC在调节垂体前叶激素分泌中的拟议作用提供了一条可能的调节控制途径。

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