The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice

© 2008 Lei et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice

<p>Abstract</p> <p>Background</p> <p>Sidestream smoke is closely associated with airway inflammation and hyperreactivity. The present study was designed to investigate if the Raf-1 inhibitor GW5074 and the anti-inflammatory drug dexamethasone suppress airway hyperreactivity in a mouse model of sidestream smoke exposure.</p> <p>Methods</p> <p>Mice were repeatedly exposed to smoke from four cigarettes each day for four weeks. After the first week of the smoke exposure, the mice received either dexamethasone intraperitoneally every other day or GW5074 intraperitoneally every day for three weeks. The tone of the tracheal ring segments was recorded with a myograph system and concentration-response curves were obtained by cumulative administration of agonists. Histopathology was examined by light microscopy.</p> <p>Results</p> <p>Four weeks of exposure to cigarette smoke significantly increased the mouse airway contractile response to carbachol, endothelin-1 and potassium. Intraperitoneal administration of GW5074 or dexamethasone significantly suppressed the enhanced airway contractile responses, while airway epithelium-dependent relaxation was not affected. In addition, the smoke-induced infiltration of inflammatory cells and mucous gland hypertrophy were attenuated by the administration of GW5074 or dexamethasone.</p> <p>Conclusion</p> <p>Sidestream smoke induces airway contractile hyperresponsiveness. Inhibition of Raf-1 activity and airway inflammation suppresses smoking-associated airway hyperresponsiveness.</p

Pro-Leu-GlyNH2 affects dopamine and noradrenaline utilization in rat limbic-forebrain nuclei

The effects of Pro-Leu-GlyNH2 (PLG), administered i.c.v. in doses of 3.5, 35, 350 and 3500 pmol, were studied on the α-MPT-induced disappearance of catecholamines in microdissected rat brain nuclei. PLG, dose-dependently, increased dopamine disappearance in the nucleus caudatus and globus pallidus, whereas a decrease in dopamine disappearance was observed in the nucleus dorsomedialis. Noradrenaline disappearance was decreased in the medial septal nucleus, anterior hypothalamic area and lateral amygdala. A tendency towards an increase in noradrenaline disappearance was observed in the nucl. supraopticus. These data show that PLG has a central site of action. The effects of PLG on dopamine disappearance are comparable to those previously found with vasopressin, while the effects of PLG on noradrenaline utilization show a striking similarity with those previously obtained with oxytocin