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用光学显微镜放射自显影法对大鼠肾脏中β肾上腺素能受体亚型进行定位。

Localization of beta adrenoceptor subtypes in rat kidney by light microscopic autoradiography.

作者信息

Summers R J, Stephenson J A, Kuhar M J

出版信息

J Pharmacol Exp Ther. 1985 Feb;232(2):561-9.

PMID:2982017
Abstract

The characteristics and localization of beta adrenoceptor subtypes in rat kidney sections have been examined using [125I]cyanopindolol and in vitro labeling combined with autoradiography. Binding was stereoselective since the (-)-isomers of propranolol and pindolol were some two orders of magnitude more effective as competitors than the (+)-isomers. Competition curves obtained using the subtype selective antagonists ICI 118,551 (beta-2) and betaxolol (beta-1) had low pseudo Hill coefficients and were resolved into two distinct components representing beta-1 (63%) and beta-2 adrenoceptors (37%). Combined autoradiographic and histochemical studies using nuclear emulsion-coated coverslips and alkaline phosphatase staining showed that the majority of receptors were in the renal cortex and in the outer band of the medulla with fewer receptors associated with the inner medulla, papilla and renal blood vessels. Delineation of beta-1 and beta-2 adrenoceptor subtypes with the selective antagonists betaxolol and ICI 118,551 indicated that the highly localized receptors were predominately of the beta-1 subtype, associated with glomeruli and with tubules that from their staining characteristics and topography represent distal and cortical collecting tubules with few if any receptors associated with proximal tubules. Beta-2 adrenoceptors were more diffusely distributed in the cortex and there were minor areas of localization in the inner medulla. Although some glomerular beta adrenoceptors probably play a role in control of renin release, their distribution throughout this structure indicates that they also control other functions. The distribution of beta adrenoceptors in tubules corresponds well with the known distribution of beta adrenoceptor-stimulated adenylate cyclase in rat kidney and indicates that these receptors subserve a physiological function.

摘要

利用[125I]氰基吲哚洛尔以及体外标记结合放射自显影技术,对大鼠肾切片中β肾上腺素能受体亚型的特征和定位进行了研究。结合具有立体选择性,因为普萘洛尔和吲哚洛尔的(-)-异构体作为竞争者的效力比(+)-异构体高约两个数量级。使用亚型选择性拮抗剂ICI 118,551(β-2)和倍他洛尔(β-1)获得的竞争曲线具有低的伪希尔系数,并被解析为代表β-1(63%)和β-2肾上腺素能受体(37%)的两个不同成分。使用核乳胶包被盖玻片和碱性磷酸酶染色的放射自显影和组织化学联合研究表明,大多数受体位于肾皮质和髓质外层,与肾髓质内层、乳头和肾血管相关的受体较少。用选择性拮抗剂倍他洛尔和ICI 118,551对β-1和β-2肾上腺素能受体亚型的描绘表明,高度定位的受体主要是β-1亚型,与肾小球以及从其染色特征和形态学来看代表远端和皮质集合小管的小管相关,近端小管几乎没有或没有与之相关的受体。β-2肾上腺素能受体在皮质中分布更分散,在内髓质中有少量定位区域。虽然一些肾小球β肾上腺素能受体可能在肾素释放的控制中起作用,但其在整个结构中的分布表明它们也控制其他功能。β肾上腺素能受体在小管中的分布与大鼠肾脏中β肾上腺素能受体刺激的腺苷酸环化酶的已知分布非常吻合,表明这些受体具有生理功能。

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