Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist.
Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have anti-inflammatory properties and in some instances smooth muscle relaxing effects. Since inflammation and airway smooth muscle contraction are two major components of asthma, the present authors investigated the effects of DMPP on airway inflammation and airway resistance in a mouse model of asthma. Mice were sensitised and challenged with ovalbumin (OVA) and treated either intraperitoneally or intranasally with DMPP. The effect of DMPP was tested on airway inflammation, airway resistance and on the increase of intracellular calcium in bronchial smooth muscle cells. DMPP given either during sensitisation, OVA challenges or throughout the protocol prevented lung inflammation and decreased the serum level of OVA specific immunoglobulin E. DMPP administration reduced the number of total cells, lymphocytes and eosinophils in the bronchoalveolar lavage (BAL) fluid. Intranasal DMPP administration was as effective as dexamethasone (DEXA) in reducing total cell count and eosinophil counts in BAL fluid. DMPP, but not DEXA, reduced tissue inflammation. Intranasal DMPP, given 10 min before the test, reduced airway responsiveness to metacholine. DMPP also reduced the increase in intracellular calcium in response to bradykinin. In conclusion, these results show that 1,1-dimethyl-4-phenylpiperazinium reduces lung inflammation and prevents airway hyperresponsiveness in the mouse model of asthma.
Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Québec, Canada.
M-R
MR
Blanchet
E
E
Israël-Assayag
Y
Y
Cormier
D000403:Airway Resistance / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000473:pathology; D001707:Biopsy, Needle; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis* / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D011336:Probability; D011897:Random Allocation; D012016:Reference Values
D007073:Immunoglobulin E; D004246:Dimethylphenylpiperazinium Iodide; D010047:Ovalbumin