Renal action of atrial natriuretic peptide

心房钠尿肽的肾作用

• 批准号: 61480121
• 负责人: IMAI Masashi
• 金额: $ 3.71万
• 依托单位: National Cardiovascular Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480121/
• 关键词: Atrial natriuretic peptide; Renal tubule; Glomerulus; Henle's loop; Renal medullary blood flow; Autoradiography; Receptor; ANP; 尿中Na排泄; 平滑筋; エンドペプチターゼ; 心房性ナトリウム利尿ペプチド; 集合管; 腎髄質; バゾプレシン; 心房性Na利尿ポリペプチド; ANF; 直血管; 受容体; オートラジオグラフィ

Interactions between atrial natriuretic peptide(ANP) and the kidney were examined by various approaches including autoradiography, receptor binding study, clearance study, in vitro microperfusion of renal tubules, and others. The following 5 major results were obtained: (1) By sutoradiography, we demonstrated that receptors for ANP were distributed in the glomeruli (foot processes of epithelial cells), vascular bundles and inner medullary collecting tubules. By solubilizing ANP-receptors labeled by photoaffinity method, we found that molecular size of the receptors in the kidney is 65 kD wherease the aorta and the adrenal grand contain two kinds of receptors having different molecular size, 65 kD and 140 kD. (2) The structure-activity relationship, examined by using -hANP analogs, showed that amino acids in N-termainus, amino acid at 12th position and ring structure are essential for physiological effects. (3) Intrarenal arterial administration of ANP in combination with acetyl choline or secretin suggested that effects of ANP are mediated in part by its renal vascular action. (4) In vitro microperfusion of isolated renal tubules failed to demonstrate any effects on NaCl and water transport in segments of Henle's loop and inner medullary collecting tubule. (5) Degradation of ANP, inhibitable with phospholamidone, was localized to both the glomeruli and the proximal tubules.

通过放射自显影、受体结合研究、清除率研究、肾小管体外微灌注等多种方法研究了房利钠肽（ANP）与肾脏的相互作用。(1)通过x线摄影，我们发现ANP受体分布在肾小球（上皮细胞足突）、维管束和髓内集合小管中。通过溶解光亲和法标记的anp受体，我们发现肾脏中的受体分子大小为65 kD，而主动脉和肾上腺中含有65 kD和140 kD两种不同分子大小的受体。(2)利用-hANP类似物对其构效关系进行了分析，结果表明，n端氨基酸、12位氨基酸和环状结构对其生理作用至关重要。(3) ANP联合乙酰胆碱或分泌素经肾动脉给药表明ANP的作用部分是通过其肾血管作用介导的。(4)离体肾小管体外微灌注未发现对Henle’s袢和内髓集管段的NaCl和水运输有任何影响。(5)磷胺酮可抑制ANP的降解，其降解局限于肾小球和近端小管。

项目成果

古関千寿子他: 腎と透析. 22. 597-605 (1987)

Chizuko Koseki 等人：肾脏和透析。22. 597-605 (1987)

Koseki C;Hayashi Y;Ohnuma N;Imai M: Biochem,Biophys.Res.Commun.136. 200-207 (1986)

Koseki C；Hayashi Y；Ohnuma N；Imai M：Biochem，Biophys.Res.Commun.136。

Akabane S; Matsushima Y; Torikai S; Imai M; Ito K:"Additive effects of atrial natriuretic polypeptide to renal vasodilating agents in the anesthetized dog." Eur J Pharmacol. 122. 181-189 (1986)

赤羽S;

Shima,M;Seino,Y;Torikai,S;Imai: Life Sci.43. 357-363 (1988)

Shima，M；Seino，Y；Torikai，S；Imai：生命科学.43。

Akabane S;Matsushima Y;Torikai S;Imai M,Ito K: Eur.J.Pharmacol.122. 181-189 (1986)

Akabane S；Matsushima Y；Torikai S；Imai M，Ito K：Eur.J.Pharmacol.122。