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心房利钠因子受体在肠系膜动脉床中的定位。与血管紧张素II和内皮素受体的比较。

Localization of atrial natriuretic factor receptors in the mesenteric arterial bed. Comparison with angiotensin II and endothelin receptors.

作者信息

De León H, Bonhomme M C, Thibault G, Garcia R

机构信息

Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Montreal University, Quebec, Canada.

出版信息

Circ Res. 1995 Jul;77(1):64-72. doi: 10.1161/01.res.77.1.64.

Abstract

Although receptors for atrial natriuretic factor (ANF) and angiotensin II (Ang II) have been reported in rat mesenteric arteries, both peptides induce weak biological responses. Endothelin-1 (ET-1) evokes a potent vasoconstriction in the mesenteric artery. To identify the tissue localization of ANF, Ang II, and ET-1 receptors, radioligand binding experiments with 125I-ANF, 125I-[Sar1,Ile8]Ang II, and 125I-ET-1 were performed in defatted mesenteric arteries and in the surrounding adipose tissue. 125I-ANF binding assays in adipose tissue showed a single class of high-affinity binding sites (Bmax, 420 +/- 16 fmol/mg protein; Kd, 343 +/- 16 pmol/L). In vascular membranes, most 125I-ANF binding was nonspecific. The majority of receptors present in adipose tissue recognized ANF, C-type natriuretic peptide (CNP), and des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANF-(4- 23) (C-ANF) with close affinities, with C-ANF competing for > 98% of the binding sites. In adipocytes, ANF and CNP stimulated cGMP generation. cGMP production by mesenteric arteries was stimulated by sodium nitroprusside but not by ANF or CNP. Autoradiographic localization of 125I-ANF and 125I-ET-1 showed that in the case of ANF, most specific binding occurred in adipocytes, whereas for ET-1, specific binding was present in both adipose tissue and mesenteric arteries. Cross-linking of 125I-ANF followed by SDS-PAGE revealed two receptor species of 130 and 70 kD in adipose membranes and none in vascular tissue. Both were completely displaced by ANF, CNP, and C-ANF. 125I-[Sar1,Ile8]Ang II binding assays in adipose tissue exhibited a single class of binding sites (Bmax, 211 +/- 4 fmol/mg protein; Kd, 520 +/- 10 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

尽管已报道大鼠肠系膜动脉中存在心房利钠因子(ANF)和血管紧张素II(Ang II)的受体,但这两种肽引发的生物学反应都较弱。内皮素-1(ET-1)可引起肠系膜动脉强烈的血管收缩。为了确定ANF、Ang II和ET-1受体的组织定位,在脱脂肠系膜动脉和周围脂肪组织中进行了用125I-ANF、125I-[Sar1,Ile8]Ang II和125I-ET-1的放射性配体结合实验。脂肪组织中的125I-ANF结合试验显示出一类单一的高亲和力结合位点(最大结合容量Bmax,420±16 fmol/mg蛋白质;解离常数Kd,343±16 pmol/L)。在血管膜中,大多数125I-ANF结合是非特异性的。脂肪组织中存在的大多数受体对ANF、C型利钠肽(CNP)和去-[Gln18,Ser19,Gly20,Leu21,Gly22]ANF-(4-23)(C-ANF)具有相近的亲和力,其中C-ANF可竞争>98%的结合位点。在脂肪细胞中,ANF和CNP刺激环磷酸鸟苷(cGMP)的生成。肠系膜动脉产生cGMP受到硝普钠的刺激,但不受ANF或CNP的刺激。125I-ANF和125I-ET-1的放射自显影定位显示,就ANF而言,大多数特异性结合发生在脂肪细胞中,而对于ET-1,特异性结合存在于脂肪组织和肠系膜动脉中。125I-ANF交联后进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)显示,脂肪膜中有130和70 kD两种受体,而血管组织中没有。两者都被ANF、CNP和C-ANF完全取代。脂肪组织中的125I-[Sar1,Ile8]Ang II结合试验显示出一类单一的结合位点(Bmax,211±4 fmol/mg蛋白质;Kd,520±10 pmol/L)。(摘要截短于250字)

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