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α2-肾上腺素受体亚型在啮齿动物肾脏中的亚细胞分布。

Subcellular distribution of α2-adrenoceptor subtypes in the rodent kidney.

机构信息

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan.

Division of Research Instrument and Equipment, Life Science Research Center, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

出版信息

Cell Tissue Res. 2022 Feb;387(2):303-314. doi: 10.1007/s00441-021-03558-w. Epub 2021 Nov 27.

Abstract

Renal α2-adrenoceptors have been reported to play a role in the regulation of urinary output, renin secretion, and water and sodium excretion in the kidneys. However, the distribution of α2-adrenoceptor subtypes in the kidneys remains unclear. In this study, we aimed to investigate the localization of α2-adrenoceptor subtypes in rat kidneys using 8-week-old Sprague-Dawley rats. Immunofluorescence imaging revealed that both α2A- and α2B-adrenoceptors were expressed in the basolateral, but not apical, membrane of the epithelial cells of the proximal tubules. We also found that α2A- and α2B-adrenoceptors were not expressed in the glomeruli, collecting ducts, or the descending limb of the loop of Henle and vasa recta. In contrast, α2C-adrenoceptors were found to be localized in the glomeruli and lumen of the cortical and medullary collecting ducts. These results suggest that noradrenaline may act on the basement membrane of the proximal tubules through α2A- and α2B-adrenoceptors. Moreover, noradrenaline may be involved in the regulation of glomerular filtration and proteinuria through the induction of morphological changes in mesangial cells and podocytes via α2C-adrenoceptors. In the collecting ducts, urinary noradrenaline may regulate morphological changes of the microvilli through α2C-adrenoceptors. Our findings provide an immunohistochemical basis for understanding the cellular targets of α2-adrenergic regulation in the kidneys. This may be used to devise therapeutic strategies targeting α2-adrenoceptors.

摘要

肾脏的α2-肾上腺素受体在调节尿输出、肾素分泌以及肾脏中的水和钠排泄方面发挥作用。然而,肾脏中α2-肾上腺素受体亚型的分布仍不清楚。在这项研究中,我们旨在使用 8 周龄的 Sprague-Dawley 大鼠研究α2-肾上腺素受体亚型在大鼠肾脏中的定位。免疫荧光成像显示,α2A-和α2B-肾上腺素受体均表达在近端肾小管的基底外侧膜,但不在顶膜上。我们还发现,α2A-和α2B-肾上腺素受体不在肾小球、集合管或亨利氏袢降支和直小血管中表达。相比之下,α2C-肾上腺素受体定位于肾小球和皮质及髓质集合管的管腔中。这些结果表明,去甲肾上腺素可能通过α2A-和α2B-肾上腺素受体作用于近端肾小管的基底膜。此外,去甲肾上腺素可能通过α2C-肾上腺素受体诱导系膜细胞和足细胞的形态变化,参与肾小球滤过和蛋白尿的调节。在集合管中,尿去甲肾上腺素可能通过α2C-肾上腺素受体调节微绒毛的形态变化。我们的发现为理解肾脏中α2-肾上腺素能调节的细胞靶标提供了免疫组织化学基础。这可能用于设计针对α2-肾上腺素受体的治疗策略。

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