Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5‐HT1B receptors via the Raf/ERK/MAPK pathway in rats. (4th September 2012)

• Record Type: Journal Article
• Authors: Cao, L.; Xu, C. B.; Zhang, Y.; Cao, Y. X.; Edvinsson, L.
• Is Part Of: Acta physiologica. Volume 207:Number 1(2013:Jan.)
• Page Start: 183
• Page End: 193
• Publication Date: 2012-09-04
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/j.1748-1716.2012.02478.x
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha2478-abs-0001"> <title>Abstract</title> <sec id="apha2478-sec-0001" sec-type="section"> <title>Aim</title> <p>Cigarette smoke exposure increases the risk of stroke. Upregulation of 5‐hydroxytryptamine 1B (5‐HT<sub>1</sub><sub>B</sub>) receptors is associated with the pathogenesis of cerebral ischaemia. This study examined the hypothesis that the expression of 5‐HT<sub>1</sub><sub>B</sub> receptors is altered in brain vessels after secondhand smoke (SHS) exposure.</p> </sec> <sec id="apha2478-sec-0002" sec-type="section"> <title>Methods</title> <p>Rats were exposed to SHS <italic>in vivo</italic> 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<sub>1</sub><sub>B</sub> 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.</p> </sec> <sec id="apha2478-sec-0003" sec-type="section"> <title>Results</title> <p>The results showed that SHS exposure shifted the 5‐HT<sub>1</sub><sub>B</sub> 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<sub>1</sub><sub>B</sub> receptors in SHS‐exposed rats. Immunostaining revealed that the 5‐HT<sub>1</sub><sub>B</sub> 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<sub>1</sub><sub>B</sub> receptor upregulation.</p> </sec> <sec id="apha2478-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Secondhand smoke exposure upregulates cerebrovascular 5‐HT<sub>1</sub><sub>B</sub> receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation.</p> </sec> </abstract>