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Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5‐ HT 1 B receptors via the R af/ ERK / MAPK pathway in rats
Author(s) -
Cao L.,
Xu C. B.,
Zhang Y.,
Cao Y. X.,
Edvinsson L.
Publication year - 2013
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2012.02478.x
Subject(s) - downregulation and upregulation , receptor , mapk/erk pathway , myograph , kinase , western blot , signal transduction , endocrinology , chemistry , medicine , biology , contraction (grammar) , biochemistry , gene
Aim Cigarette smoke exposure increases the risk of stroke. Upregulation of 5‐hydroxytryptamine 1 B (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 m RNA 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 R af/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 m RNA 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 R af‐1 and ERK 1/2 proteins. The administration of a R af‐1 inhibitor GW 5074 attenuated the 5‐ HT 1 B receptor upregulation. Conclusion Secondhand smoke exposure upregulates cerebrovascular 5‐ HT 1 B receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation.