AN OXIDIZED ANALOG OF ALPHA-HUMAN ATRIAL NATRIURETIC POLYPEPTIDE IS A SELECTIVE AGONIST FOR THE ATRIAL-NATRIURETIC-POLYPEPTIDE CLEARANCE RECEPTOR WHICH LACKS A GUANYLATE-CYCLASE

被引：13

作者：

KOYAMA, S ^{[1
]}

TERAI, T ^{[1
]}

INOUE, T ^{[1
]}

INOMATA, K ^{[1
]}

TAMURA, K ^{[1
]}

KOBAYASHI, Y ^{[1
]}

KYOGOKU, Y ^{[1
]}

KOBAYASHI, M ^{[1
]}

机构：

[1] OSAKA UNIV,INST PROT RES,SUITA,OSAKA 565,JAPAN

来源：

EUROPEAN JOURNAL OF BIOCHEMISTRY | 1992年 / 203卷 / 03期

关键词：

D O I：

10.1111/j.1432-1033.1992.tb16566.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The differences in biological functions between alpha-human atrial natriuretic polypeptide (alpha-hANP) and its oxidized analog, MetSO-alpha-hANP, have been investigated. Analysis of the ANP receptor subtypes by affinity labeling has shown that a bovine pulmonary aortic endothelial cell line (CPAE cells) primarily expresses ANP-R1 (R, receptor) coupled to particulate guanylate cyclase, while Hela cells from human cervical carcinoma predominantly express ANP-R2, which lacks a guanylate cyclase. alpha-hANP could bind to both ANP receptor subtypes with high affinity, while MetSO-alpha-hANP showed more selective binding to ANP-R2 than to ANP-R1. The activity of MetSO-alpha-hANP for stimulation of guanylate cyclase coupled to ANP-R1 was about 520-fold less than that of alpha-hANP (median effective dose = 2.5 nM for alpha-hANP, 1.3-mu-M for MetSO-alpha-hANP), indicating that MetSO-alpha-hANP was a partial agonist for this receptor. While this oxidized analog could inhibit the cAMP production through ANP-R2 with 0.15 times the activity of alpha-hANP (median concentration = 0.31 nM for alpha-hANP, 2.0 nM for MetSO-alpha-hANP). In in vivo studies, the diuretic activity of MetSO-alpha-hANP was 25-100-fold less than that of alpha-hANP. In addition, MetSO-alpha-hANP could potentiate the diuretic activity of alpha-hANP that was also caused by C-ANF4-23, a specific agonist for ANP-R2. These results demonstrate that MetSO-alpha-hANP can act as an agonist more selective for ANP-R2 than for ANP-R1, both in vivo and in vitro. The relationship between receptor selectivities and the conformation of alpha-hANP or MetSO-alpha-hANP was also discussed.

引用

页码：425 / 432

页数：8

共 27 条

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