de Leon H, Bonhomme M C, Garcia R
Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Quebec, Canada.
J Hypertens. 1994 May;12(5):539-48.
Atrial natriuretic factor (ANF) receptor subtypes were quantitated by radioligand studies in three different rat renal isolated tissues: preglomerular vessels, glomeruli and papillae.
In preglomerular vessels 100% of [125I]-ANF binding was displaced with high affinity by ANF. C-ANF (des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP(4- 23)) a specific ligand for ANP-C receptors, displaced 30% of total binding with a lower affinity than ANF. C-type natriuretic peptide (CNP) displaced [125I]-ANF binding in a biphasic manner, indicating that it binds to two sites with affinities three orders of magnitude apart. When CNP was incubated in the presence of 0.1 mumol/l C-ANF to saturate ANP-C receptors, the high-affinity binding site vanished and maximum binding decreased to 70%, suggesting that CNP binds with high affinity to ANP-C receptors. Since the ANP-A receptor has little or no avidity for CNP, it is probably the low-affinity binding site. CNP and C-ANF displaced most [125I]-[Tyr]CNP(1-22) binding with very close affinities, indicating that CNP binds primarily preglomerular vascular ANP-C receptors. In glomeruli CNP behaved similarly to C-ANF in its ability to displace approximately 85% of [125I]-ANF binding; the remaining 15% was completely displaced by ANF. C-ANF and CNP inhibited 100% of [125I]-[Tyr]CNP(1-22) binding. Both findings suggest that [125I]-[Tyr]CNP(1-22) binds ANP-C receptors exclusively. In renal papillae no displacement of [125I]-ANF by C-ANF was observed, and CNP was bound to ANP-A receptors with the same very low affinity as in preglomerular vessels. The absence of [125I]-[Tyr]CNP(1-22) binding to papillary membranes indicates that ANP-B receptors are not expressed in that tissue. Unlike ANF, CNP stimulated cGMP production in glomeruli and papillae only at extremely high, supraphysiological concentrations.
The present results suggest that ANP-B receptors either are absent or are present in undetectable amounts in rat renal preglomerular vessels, glomeruli and papillae.
通过放射性配体研究对三种不同的大鼠肾分离组织(肾小体前血管、肾小球和乳头)中的心房钠尿肽(ANF)受体亚型进行定量分析。
在肾小体前血管中,100%的[125I]-ANF结合可被ANF以高亲和力取代。C-ANF(去[Gln18,Ser19,Gly20,Leu21,Gly22]ANP(4-23)),一种ANP-C受体的特异性配体,以低于ANF的亲和力取代了30%的总结合。C型钠尿肽(CNP)以双相方式取代[125I]-ANF结合,表明它与两个亲和力相差三个数量级的位点结合。当CNP在0.1 μmol/L C-ANF存在下孵育以饱和ANP-C受体时,高亲和力结合位点消失,最大结合减少到70%,这表明CNP以高亲和力与ANP-C受体结合。由于ANP-A受体对CNP几乎没有或没有亲和力,所以它可能是低亲和力结合位点。CNP和C-ANF以非常接近的亲和力取代了大部分[125I]-[Tyr]CNP(1-22)结合,表明CNP主要与肾小体前血管ANP-C受体结合。在肾小球中,CNP在取代约85%的[125I]-ANF结合方面的表现与C-ANF相似;其余15%被ANF完全取代。C-ANF和CNP抑制了100%的[125I]-[Tyr]CNP(1-22)结合。这两个发现都表明[125I]-[Tyr]CNP(1-22)仅与ANP-C受体结合。在肾乳头中,未观察到C-ANF对[125I]-ANF的取代,并且CNP以与肾小体前血管中相同的非常低的亲和力与ANP-A受体结合。肾乳头膜上不存在[125I]-[Tyr]CNP(1-22)结合表明ANP-B受体在该组织中不表达。与ANF不同,CNP仅在极高的、超生理浓度下刺激肾小球和乳头中的cGMP产生。
目前的结果表明,大鼠肾小体前血管、肾小球和乳头中要么不存在ANP-B受体,要么其含量低于检测水平。