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心房利钠肽和脑利钠肽在肾脏和心脏中共享结合位点。

Atrial and brain natriuretic peptides share binding sites in the kidney and heart.

作者信息

Oehlenschlager W F, Baron D A, Schomer H, Currie M G

机构信息

Department of Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.

出版信息

Eur J Pharmacol. 1989 Feb 28;161(2-3):159-64. doi: 10.1016/0014-2999(89)90838-8.

Abstract

We examined the distribution of binding sites for atrial natriuretic peptide (ANP) and the recently discovered brain natriuretic peptide (BNP) in rat kidney and heart by receptor autoradiography. In frozen kidney sections, both 125I-ANP and 125I-BNP exhibited localized binding to cortical glomeruli. The binding of each radiolabeled peptide was abolished by inclusion of either excess (1 microM) unlabeled ANP or excess unlabeled BNP, suggesting that ANP and BNP share cortical glomerular binding sites. In frozen cardiac sections, ANP and BNP binding sites were localized to the endothelium of the endomural channels and endocardium. As was the case for kidney, binding of each peptide at these sites was abolished by the presence of excess unlabeled ANP or BNP, suggesting that these natriuretic peptides share binding sites in the heart as well. To explore further the possibility that ANP and BNP utilize the same receptor(s), we performed competitive binding experiments using cultured pulmonary artery endothelial (CPAE) cells. ANP and BNP competitively displaced one another with equivalent IC50 values from CPAE cell binding sites. Furthermore, both ANP and BNP elevated the levels of cGMP, a putative second messenger for ANP, in these cells. These data are consistent with the observation that BNP, like ANP, causes a natriuresis and diuresis in rats, and suggest that BNP may possess other biological activities known for ANP.

摘要

我们通过受体放射自显影术研究了心房利钠肽(ANP)和最近发现的脑利钠肽(BNP)在大鼠肾脏和心脏中的结合位点分布。在冷冻的肾脏切片中,¹²⁵I-ANP和¹²⁵I-BNP均表现出与皮质肾小球的局部结合。通过加入过量(1微摩尔)未标记的ANP或过量未标记的BNP,可消除每种放射性标记肽的结合,这表明ANP和BNP共享皮质肾小球结合位点。在冷冻的心脏切片中,ANP和BNP结合位点定位于心内膜通道和心内膜的内皮。与肾脏情况相同,在这些位点每种肽的结合因过量未标记的ANP或BNP的存在而被消除,这表明这些利钠肽在心脏中也共享结合位点。为了进一步探究ANP和BNP是否利用相同受体的可能性,我们使用培养的肺动脉内皮(CPAE)细胞进行了竞争性结合实验。ANP和BNP以等效的IC50值从CPAE细胞结合位点相互竞争性取代。此外,ANP和BNP均提高了这些细胞中cGMP的水平,cGMP是ANP的一种假定的第二信使。这些数据与BNP与ANP一样在大鼠中引起利钠和利尿的观察结果一致,并表明BNP可能具有已知的ANP的其他生物学活性。

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