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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

cerebral artery

5-HT1B receptors

Raf

ERK

MAPK pathway

secondhand

smoke exposure

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)