Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi

被引：22

作者：

Granström B.W. ^{[1
]}

Xu C.-B. ^{[1
]}

Nilsson E. ^{[1
]}

Vikman P. ^{[1
]}

Edvinsson L. ^{[1
]}

机构：

[1] Department of Medicine, Lund University, Lund

来源：

BMC Pulmonary Medicine | / 6卷 / 1期

关键词：

Nicotine; Bosentan; Contractile Response; Bronchial Smooth Muscle; Bronchial Segment;

D O I：

10.1186/1471-2466-6-6

中图分类号：

学科分类号：

摘要：

Background: Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP) from cigarette smoke, to nicotine and to DMSO, respectively. Methods: Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ETB receptors) and endothelin-I (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-I was introduced, the ETB receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ETA receptors. ETA and ETB receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ETA and ETB receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies. Results: After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ETA and ETB receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ETA and ETB receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ETA and ETB receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism. Conclusion: The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism. © 2006 Granström et al; licensee BioMed Central Ltd.

引用

共 37 条

[1]

Ezzati M., Hoorn S.V., Rodgers A., Lopez A.D., Mathers C.D., Murray C.J., Estimates of global and regional potential health gains from reducing multiple major risk factors, Lancet, 362, pp. 271-280, (2003)

[2]

Patel B.D., Luben R.N., Welch A.A., Bingham S.A., Khaw K.T., Day N.E., Lomas D.A., Wareham N.J., Childhood smoking is an independent risk factor for obstructive airways disease in women, Thorax, 59, pp. 682-686, (2004)

[3]

Smith C.J., Fischer T.H., Particulate and vapor phase constituents of cigarette mainstream smoke and risk of myocardial infarction, Atherosclerosis, 158, pp. 257-267, (2001)

[4]

Sekhon H.S., Wright J.L., Churg A., Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries, Am J Physiol, 267, (1994)

[5]

Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T., A novel potent vasoconstrictor peptide produced by vascular endothelial cells, Nature, 332, pp. 411-415, (1988)

[6]

Rozengurt N., Springall D.R., Polak J.M., Localization of endothelinlike immunoreactivity in airway epithelium of rats and mice, J Pathol, 160, pp. 5-8, (1990)

[7]

Mattoli S., Mezzetti M., Riva G., Allegra L., Fasoli A., Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells, Am J Respir Cell Mol Biol, 3, pp. 145-151, (1990)

[8]

Henry P.J., Endothelin-I (ET-I)-induced contraction in rat isolated trachea: Involvement of ETA and ETB receptors and multiple signal transduction systems, Br J Pharmacol, 110, pp. 435-441, (1993)

[9]

Goldie R.G., D'Aprile A.C., Self G.J., Rigby P.J., Henry P.J., The distribution and density of receptor subtypes for endothelin-I in peripheral lung of the rat, guinea-pig and pig, Br J Pharmacol, 117, pp. 729-735, (1996)

[10]

Goldie R.G., Henry P.J., Knott P.G., Self G.J., Luttmann M.A., Hay D.W., Endothelin-I receptor density, distribution, and function in human isolated asthmatic airways, Am J Respir Crit Care Med, 152, pp. 1653-1658, (1995)

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