|Reference : Modulation of acetylcholine, capsaicin and substance P effects by histamine H3 receptors...|
|Scientific journals : Article|
|Human health sciences : Pharmacy, pharmacology & toxicology|
|Modulation of acetylcholine, capsaicin and substance P effects by histamine H3 receptors in isolated perfused rabbit lungs.|
|Delaunois, Annie [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]|
|Gustin, Pascal [Université de Liège - ULg > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie >]|
|Garbarg, M. [> > > >]|
|Ansay, Michel [Université de Liège - ULg > Services généraux (Faculté de médecine vétérinaire) > Relations académiques et scientifiques (Méd. vétérinaire) >]|
|European Journal of Pharmacology|
|[en] Acetylcholine/metabolism/toxicity ; Animals ; Capillary Permeability/drug effects ; Capsaicin/metabolism/toxicity ; Dose-Response Relationship, Drug ; Drug Interactions ; Endothelium/drug effects/metabolism ; Female ; Histamine Agonists/pharmacology ; Histamine Antagonists/pharmacology ; Imidazoles/pharmacology ; Lung/drug effects ; Male ; Nerve Fibers/drug effects/metabolism ; Piperidines/pharmacology ; Pulmonary Edema/chemically induced/metabolism ; Rabbits ; Receptors, Histamine H3/drug effects/metabolism ; Serotonin/metabolism/toxicity ; Substance P/metabolism/toxicity ; Thiourea/analogs & derivatives/pharmacology|
|[en] The modulatory role of histamine H3 receptors in pulmonary oedema induced by acetylcholine, capsaicin and by exogenous substance P was investigated in isolated, ventilated rabbit lungs. Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). Acetylcholine (10(-8) to 10(-4) M), substance P (10(-10) to 10(-6) M), capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) induced an increase in the Kf,c. Carboperamide, a novel histamine H3 receptor antagonist, induced a significant leftward shift of the concentration-response curve to acetylcholine and also enhanced the effect of capsaicin on the Kf,c, while it had no significant effect on the response to substance P and 5-HT. Imetit, a new histamine H3 receptor agonist, strongly inhibited the effects of acetylcholine and capsaicin. Imetit also strongly protected the lung against substance P effects but did not prevent the 5-HT-induced increase in the Kf,c. Carboperamide completely blocked the inhibitory effect of Imetit on the acetylcholine response. (R)-alpha-Methylhistamine, an other histamine H3 receptor agonist, had the same protective effect against acetylcholine response as Imetit. We conclude that histamine H3 receptors could protect the lung against acetylcholine- and capsaicin-induced oedema via a prejunctional modulatory effect on the C-fibres. However, since the response to exogenous substance P was also inhibited by histamine H3 receptor stimulation, the presence of such receptors at a postsynaptic level, probably on mast cells, was also suggested.|
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