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

Granström, Bengt LU ; Xu, Cang-Bao LU ; Nilsson, Elisabeth LU ; Vikman, Petter LU and Edvinsson, Lars LU (2006) In BMC Pulmonary Medicine 6(6).
Abstract
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-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ETB receptors... (More)
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-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Pulmonary Medicine
volume
6
issue
6
publisher
BioMed Central (BMC)
external identifiers
  • scopus:33646184810
ISSN
1471-2466
DOI
10.1186/1471-2466-6-6
language
English
LU publication?
yes
id
c6ce4d27-5e00-40a4-9bff-707a3adae97b (old id 1137045)
date added to LUP
2016-04-01 15:34:28
date last changed
2021-08-25 02:42:36
@article{c6ce4d27-5e00-40a4-9bff-707a3adae97b,
  abstract     = {Background<br/><br>
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.<br/><br>
<br/><br>
Methods<br/><br>
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-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 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.<br/><br>
<br/><br>
Results<br/><br>
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.<br/><br>
<br/><br>
Conclusion<br/><br>
The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism.},
  author       = {Granström, Bengt and Xu, Cang-Bao and Nilsson, Elisabeth and Vikman, Petter and Edvinsson, Lars},
  issn         = {1471-2466},
  language     = {eng},
  number       = {6},
  publisher    = {BioMed Central (BMC)},
  series       = {BMC Pulmonary Medicine},
  title        = {Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi.},
  url          = {http://dx.doi.org/10.1186/1471-2466-6-6},
  doi          = {10.1186/1471-2466-6-6},
  volume       = {6},
  year         = {2006},
}