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

• Main Authors: Vikman Petter, Nilsson Elisabeth, Xu Cang-Bao, Granström Bengt W, Edvinsson Lars
• Format: Article
• Language: English
• Published: BMC 2006-03-01
• Series: BMC Pulmonary Medicine
• Online Access: http://www.biomedcentral.com/1471-2466/6/6

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 ET_Breceptors) and endothelin-1 (an ET_Aand ET_Breceptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ET_Breceptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ET_Areceptors. ET_Aand ET_Breceptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ET_Aand ET_Breceptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies.</p> <p>Results</p> <p>After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ET_Aand ET_Breceptors, 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 ET_Aand ET_Breceptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ET_Aand ET_Breceptors 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.</p> <p>Conclusion</p> <p>The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism.</p>