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大鼠肾脏近端小管中的α-和β-肾上腺素能受体

Alpha- and beta-adrenergic receptors in proximal tubules of rat kidney.

作者信息

Sundaresan P R, Fortin T L, Kelvie S L

机构信息

Department of Pharmacology, University of Rochester Medical Center, New York 14642.

出版信息

Am J Physiol. 1987 Nov;253(5 Pt 2):F848-56. doi: 10.1152/ajprenal.1987.253.5.F848.

Abstract

Proximal tubules were isolated from the rat kidney by collagenase digestion of the cortical tissue followed by Percoll gradient centrifugation. Microscopic and hormone-stimulated adenylate cyclase activity studies proved the purity of the preparation. [3H]Prazosin, [3H]rauwolscine, and [125I]iodocyanopindolol were used to identify and quantitate respectively the alpha 1-, alpha 2- and beta-adrenergic receptors. Proximal tubular (F4) particulate fraction was compared against other cortical nephron segment (F1, F2) fractions and the total collagenase-digested cortex particulate suspension (Ft). Proximal tubules were enriched in alpha 1- and alpha 2-adrenergic receptors compared with Ft (alpha 1-receptor, 100.4 +/- 4.5 vs. 87.4 +/- 4.9; alpha 2-receptor, 250 +/- 16.2 vs. 185.1 +/- 12 fmol/mg protein). The fractions enriched in glomeruli and distal tubular segments (F1, F2) had relatively low concentrations of alpha 1- and alpha 2-adrenergic receptors. In contrast, beta-adrenergic receptor concentration in the proximal tubules was approximately 25% of that in the Ft fraction and approximately 10% of that in the F1 fraction. Isoproterenol-stimulated adenylate cyclase activities in the different fractions corroborated well with the pattern suggested by the [125I]iodocyanopindolol binding studies. Our results suggest that whole-cortex preparation radioligand binding studies may reflect proximal tubular alpha 1- and alpha 2-adrenergic receptor changes quite well. They may, however, miss or give erroneous impressions about beta-adrenergic receptor changes occurring in different cortical nephron segments.

摘要

通过胶原酶消化皮质组织,随后进行 Percoll 梯度离心,从大鼠肾脏中分离出近端小管。显微镜检查和激素刺激的腺苷酸环化酶活性研究证明了制备物的纯度。[3H]哌唑嗪、[3H]育亨宾和[125I]碘氰吲哚洛尔分别用于鉴定和定量α1、α2和β肾上腺素能受体。将近端小管(F4)微粒部分与其他皮质肾单位节段(F1、F2)部分以及总胶原酶消化的皮质微粒悬浮液(Ft)进行比较。与 Ft 相比,近端小管中α1和α2肾上腺素能受体富集(α1受体,100.4±4.5对87.4±4.9;α2受体,250±16.2对185.1±12 fmol/mg 蛋白)。富含肾小球和远端小管节段的部分(F1、F2)中α1和α2肾上腺素能受体浓度相对较低。相比之下,近端小管中β肾上腺素能受体浓度约为 Ft 部分的 25%,约为 F1 部分的 10%。不同部分中异丙肾上腺素刺激的腺苷酸环化酶活性与[125I]碘氰吲哚洛尔结合研究表明的模式非常吻合。我们的结果表明,全皮质制备物放射性配体结合研究可能很好地反映近端小管α1和α2肾上腺素能受体的变化。然而,它们可能会遗漏或对不同皮质肾单位节段中发生的β肾上腺素能受体变化产生错误印象。

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