期刊
PULMONARY PHARMACOLOGY & THERAPEUTICS
卷 28, 期 1, 页码 68-76出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pupt.2013.11.005
关键词
Prostaglandin E-2; Salbutamol; Endothelin-1; Intrapulmonary airways; Bronchodilation; Calcium sensitivity
资金
- University of Melbourne Research Grant Support Scheme
- NHMRC Project Grants [509239, 1041575]
- May Stewart Bursary from the University of Melbourne
- Australian Postgraduate Award
Background: Current asthma therapy may not adequately target contraction of smaller intrapulmonary airways, which are a major site of airway obstruction and inflammation. The aim of this study was to characterise responses of mouse intrapulmonary airways to prostaglandin E-2 (PGE(2)) and compare its dilator efficacy with the beta(2)-adrenoceptor agonist salbutamol in situ, using lung slices. Methods: Lung slices (150 mu m) were prepared from male Balb/C mice. Changes in intrapulmonary airway lumen area were recorded and analysed by phase-contrast microscopy. Relaxation to PGE(2) and salbutamol were assessed following various levels of pre-contraction with methacholine, serotonin or endothelin-1, as well as following overnight incubation with PGE(2) or salbutamol. The mechanism of PGE(2)-mediated relaxation was explored using selective EP antagonists (EP1/2 AH6809; ER4 L-161982) and Ca2+-permeabilized slices, where airway responses are due to regulation of Ca2+-sensitivity alone. Results: PGE(2) elicited EP1/2-mediated relaxation of intrapulmonary airways. PGE(2) was more potent than salbutamol in opposing submaximal pre-contraction to all constrictors tested, and only PGE(2) opposed maximal pre-contraction with endothelin-1. Relaxation to PGE(2) was maintained when contraction to methacholine was mediated via increased Ca2+-sensitivity alone. PGE(2) was less sensitive to homologous or heterologous desensitization of its receptors than salbutamol. Conclusion: The greater efficacy and potency of PGE(2) compared to salbutamol in mouse intrapulmonary airways supports further investigation of the mechanisms underlying this improved dilator responsiveness for the treatment of severe asthma. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据