Bottari S P, Vokaer A, Kaivez E, Lescrainier J P, Vauquelin G
Acta Physiol Hung. 1985;65(3):335-46.
Both alpha- and beta-adrenergic receptors have been identified in the human myometrium by radioligand binding. Both adrenergic receptor subclasses have been shown to mediate the contractile response of the uterus upon catecholamine stimulation: alpha-adrenergic receptors cause uterine contraction while beta-adrenergic receptors induce relaxation. We have identified alpha 1- and alpha 2-adrenergic receptors in myometrial membranes using the newly developed radiolabelled specific antagonists [3H]-prazosin and [3H]-rauwolscine. This enabled us to characterize both receptor subclasses individually. Beta adrenergic receptors were identified using the radiolabelled antagonist (-)-[3H]-dihydroalprenolol. Binding of radioligands to the myometrial membrane receptors was rapid, readily reversible, of high affinity and stereoselective. The total number of alpha 1-, alpha 2- and beta-receptors was determined by Scatchard analysis of radioligand saturation binding and the beta/beta 2-receptor ratio was determined by computer analysis of the beta 2-selective antagonist ICI 118 551) (-)-[3H]-dihydroalprenolol competition binding curves. This enabled us to study the regulation of both alpha- and beta-receptor subclasses under various physiological and pharmacological conditions in the human, i.e., during different phases of the menstrual cycle, in postmenopausal women and during depo-progestin (Medroxyprogesterone acetate) therapy. Only the alpha 2- and beta 1-adrenergic receptor concentrations were found to be subjected to gonadal steroid regulation. The number of alpha 2- and beta 1-adrenergic receptors increased concomitantly with circulating plasma oestradiol levels. This effect was counteracted by progesterone. The number of alpha 1- and beta 2-adrenergic receptors was unaffected by the gonadal steroid environment. These results are an example of the heteroregulation of membrane receptors by oestrogens and progesterone and cast new light on the regulatory mechanisms involved in uterine contractility in the human.
通过放射性配体结合法已在人子宫肌层中鉴定出α-和β-肾上腺素能受体。已表明这两种肾上腺素能受体亚类均可介导子宫在儿茶酚胺刺激下的收缩反应：α-肾上腺素能受体引起子宫收缩，而β-肾上腺素能受体则诱导子宫舒张。我们使用新开发的放射性标记特异性拮抗剂[³H] - 哌唑嗪和[³H] - 萝芙木碱，在子宫肌层膜中鉴定出α1-和α2-肾上腺素能受体。这使我们能够分别对这两种受体亚类进行表征。使用放射性标记拮抗剂（-）-[³H] - 二氢心得舒鉴定β肾上腺素能受体。放射性配体与子宫肌层膜受体的结合迅速、易于逆转、具有高亲和力且具有立体选择性。通过对放射性配体饱和结合的Scatchard分析确定α1-、α2-和β受体的总数，并通过对β2选择性拮抗剂ICI 118 551（-）-[³H] - 二氢心得舒竞争结合曲线的计算机分析确定β/β2受体比率。这使我们能够研究在人类的各种生理和药理条件下，即月经周期的不同阶段、绝经后妇女以及醋酸甲羟孕酮长效避孕针治疗期间，α-和β-受体亚类的调节情况。仅发现α2-和β1-肾上腺素能受体浓度受性腺类固醇调节。α2-和β1-肾上腺素能受体的数量随循环血浆雌二醇水平的升高而增加。这种作用被孕酮抵消。α1-和β2-肾上腺素能受体的数量不受性腺类固醇环境的影响。这些结果是雌激素和孕酮对膜受体进行异源调节的一个例子，并为人类子宫收缩性的调节机制提供了新的线索。
