title: Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5-HT(1)             (B)  receptors via the Raf/ERK/MAPK pathway in rats.
abstract: OBJECTIVE
  Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1) (B) ) receptors is associated with the pathogenesis of cerebral ischaemia. This study examined the hypothesis that the expression of 5-HT(1) (B) 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(1) (B) 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(1) (B) receptor-mediated concentration-contraction curve towards the left with a markedly increased maximal contraction. Furthermore, there were significant elevations in mRNA level and protein expression of 5-HT(1) (B) receptors in SHS-exposed rats. Immunostaining revealed that the 5-HT(1) (B) 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(1) (B) receptor upregulation.
  
  
  CONCLUSIONS
  Secondhand smoke exposure upregulates cerebrovascular 5-HT(1) (B) receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation.
authors.affiliation: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: C B
authors.initials: CB
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y X
authors.initials: YX
authors.lastname: Cao
authors.forename: L
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D007211:Indoles; D010636:Phenols; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D014028:Tobacco Smoke Pollution; D012701:Serotonin; C047087:5-carboxamidotryptamine; D019908:Proto-Oncogene Proteins c-raf; C546782:Raf1 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C489251:5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone