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Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5-HT(1B) receptors via the Raf/ERK/MAPK pathway in rats.

Cao, Lei LU ; Xu, Cang-Bao LU ; Zhang, Yao LU ; Cao, Y X and Edvinsson, Lars LU (2013) In Acta Physiologica 207(1). p.183-193
Abstract
AIM:

Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1B) ) receptors is associated with the pathogenesis of cerebral ischemia. The present study examined the hypothesis that the expression of 5-HT(1B) receptors is altered in brain vessels after secondhand smoke (SHS) exposure.



METHODS:

Rats were exposed to SHS in vivo for 200 min daily for 8 weeks. The contractile responses of isolated cerebral arteries were studies by a sensitive myograph. The mRNA and protein expression for 5-HT(1B) receptors were examined by real-time PCR, Western blot and immunofluorescence, respectively. In addition, the phosphorylation of Raf/extracellular signal-regulated... (More)
AIM:

Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1B) ) receptors is associated with the pathogenesis of cerebral ischemia. The present study examined the hypothesis that the expression of 5-HT(1B) receptors is altered in brain vessels after secondhand smoke (SHS) exposure.



METHODS:

Rats were exposed to SHS in vivo for 200 min daily for 8 weeks. The contractile responses of isolated cerebral arteries were studies by a sensitive myograph. The mRNA and protein expression for 5-HT(1B) receptors were examined by real-time PCR, Western blot and immunofluorescence, respectively. In addition, the phosphorylation of Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway was evaluated.



RESULTS:

The results showed that SHS exposure shifted the 5-HT(1B) receptor-mediated concentration-contraction curve toward the left with a markedly increased maximum contraction. Furthermore, there were significant elevations in mRNA level and protein expression of 5-HT(1B) receptors in SHS-exposed rats. Immunostaining revealed that the 5-HT(1B) receptors were localized to the smooth muscle cells of cerebral arteries. SHS was also found to induce the phosphorylation of Raf-1 and ERK1/2 proteins. The administration of a Raf-1 inhibitor GW5074 attenuated the 5-HT(1B) receptor upregulation.



CONCLUSION:

SHS exposure upregulates cerebrovascular 5-HT(1B) receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cerebral artery, 5-HT1B receptors, Raf, ERK, MAPK pathway, secondhand, smoke exposure
in
Acta Physiologica
volume
207
issue
1
pages
183 - 193
publisher
Wiley-Blackwell
external identifiers
  • wos:000312340900018
  • pmid:22883081
  • scopus:84870848024
ISSN
1748-1708
DOI
10.1111/j.1748-1716.2012.02478.x
language
English
LU publication?
yes
id
44695bf9-0125-4a6b-9b3a-9807e2be69fd (old id 3047583)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22883081?dopt=Abstract
date added to LUP
2012-09-05 19:24:01
date last changed
2019-11-13 01:18:57
@article{44695bf9-0125-4a6b-9b3a-9807e2be69fd,
  abstract     = {AIM: <br/><br>
Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1B) ) receptors is associated with the pathogenesis of cerebral ischemia. The present study examined the hypothesis that the expression of 5-HT(1B) receptors is altered in brain vessels after secondhand smoke (SHS) exposure. <br/><br>
<br/><br>
METHODS: <br/><br>
Rats were exposed to SHS in vivo for 200 min daily for 8 weeks. The contractile responses of isolated cerebral arteries were studies by a sensitive myograph. The mRNA and protein expression for 5-HT(1B) receptors were examined by real-time PCR, Western blot and immunofluorescence, respectively. In addition, the phosphorylation of Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway was evaluated. <br/><br>
<br/><br>
RESULTS: <br/><br>
The results showed that SHS exposure shifted the 5-HT(1B) receptor-mediated concentration-contraction curve toward the left with a markedly increased maximum contraction. Furthermore, there were significant elevations in mRNA level and protein expression of 5-HT(1B) receptors in SHS-exposed rats. Immunostaining revealed that the 5-HT(1B) receptors were localized to the smooth muscle cells of cerebral arteries. SHS was also found to induce the phosphorylation of Raf-1 and ERK1/2 proteins. The administration of a Raf-1 inhibitor GW5074 attenuated the 5-HT(1B) receptor upregulation. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
SHS exposure upregulates cerebrovascular 5-HT(1B) receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.},
  author       = {Cao, Lei and Xu, Cang-Bao and Zhang, Yao and Cao, Y X and Edvinsson, Lars},
  issn         = {1748-1708},
  keyword      = {cerebral artery,5-HT1B receptors,Raf,ERK,MAPK pathway,secondhand,smoke exposure},
  language     = {eng},
  number       = {1},
  pages        = {183--193},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica},
  title        = {Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5-HT(1B) receptors via the Raf/ERK/MAPK pathway in rats.},
  url          = {http://dx.doi.org/10.1111/j.1748-1716.2012.02478.x},
  volume       = {207},
  year         = {2013},
}