原创力文档stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by cgrp and dissociation of et-1eta-receptor complexes刺激感觉神经终止动脉收缩的影响endothelin-1 cgrp怎样和离解et-1eta-receptor复合物.pdfVIP
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stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by cgrp and dissociation of et-1eta-receptor complexes刺激感觉神经终止动脉收缩的影响endothelin-1 cgrp怎样和离解et-1eta-receptor复合物
Stimuli of Sensory-Motor Nerves Terminate Arterial
Contractile Effects of Endothelin-1 by CGRP and
Dissociation of ET-1/ETA-Receptor Complexes
1 1 2 3
Merlijn J. P. M. T. Meens , Matthijs G. Compeer , Tilman M. Hackeng , Marc A. van Zandvoort , Ben J. A.
1 1
Janssen , Jo G. R. De Mey *
1 Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands, 2 Department of
Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands, 3 Department of Biomedical Technology,
Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
Abstract
Background: Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials
with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding
of ET-1 (i) limits reversing effects of the antagonists and (ii) can be selectively dissociated by an endogenous
counterbalancing mechanism.
Methodology/Principal findings: In isolated rat mesenteric resistance arteries, ET -antagonists, endothelium-derived
A
relaxing factors and synthetic vasodilators transiently reduced contractile effects of ET-1 but did not prevent persistent
effects of the peptide. Stimuli of peri-vascular vasodilator sensory-motor nerves such as capsaicin not only reduced but also
terminated long-lasting effects of ET-1. This was prevented by CGRP-receptor ant
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