The adrenomedullin receptor acts as clearance receptor in pulmonary circulation

被引：24

作者：

Dschietzig, T ^{[1
]}

Azad, HA ^{[1
]}

Asswad, L ^{[1
]}

Böhme, C ^{[1
]}

Bartsch, C ^{[1
]}

Baumann, G ^{[1
]}

Stangl, K ^{[1
]}

机构：

[1] Charite, Med Klin S Kardiol Angiol & Pulmol, D-10117 Berlin, Germany

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 294卷 / 02期

关键词：

adrenomedullin; receptor; endothelium; lung; isolated lungs;

D O I：

10.1016/S0006-291X(02)00474-6

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：

Adrenomedullin (AM) is a powerful pulmonary vasodilator with antimitogenic properties. We investigated the role of the AM receptor (AMR) and the calcitonin gene-related peptide type-1 receptor (CGRP1R) in regulating pulmonary vascular AM levels. The AMR antagonist hAM(22-52) (120 nmol/L) significantly elevated AM release compared with controls to 250% after 2h in isolated rat lungs and to 830% after 4h in pulmonary artery endothelial cells (PAEC). CGRPIR blockade had no effect. AMR blockade did not influence prepro-AM mRNA levels nor did inhibition of protein synthesis by cycloheximide (0.01 mg/mL) abolish the effect of the AMR antagonist. Radioligand-binding studies with PAEC membranes revealed a decrease by 44% of the AMR density in response to AMR antagonism. Altogether, the pulmonary vascular AMR represents not only a functionally active, but also a clearance receptor; its expression is constitutively stimulated by basal AM. This identifies a novel mechanism for controlling pulmonary AM levels. (C) 2002 Elsevier Science (USA). All rights reserved.

引用

页码：315 / 318

页数：4

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