[en] The pharmacological mechanisms involved in the interactions between C-fibers, cholinergic fibers and mast cells were investigated in tracheally perfused rabbit lungs by measuring the simultaneous release of substance P and histamine in lung effluents. The amounts of substance P and histamine released in lung superfusates were measured by radioimmunoassay (RIA) after administration of capsaicin and carbachol. Capsaicin (10(-4) M) induced a simultaneous increase in substance P (273 +/- 56% of baseline) and histamine (460 +/- 138%) release. Similarly, carbachol (10(-4) M) caused an increase in the release of both substance P (367 +/- 111%) and histamine (1379 +/- 351%). The effect of capsaicin was prevented by pretreating the lungs with the tachykinin NK1 receptor antagonist SR 140333 (10(-7) M), and atropine (10(-6) M). SR 140333 prevented the carbachol-induced release of substance P but not of histamine. Exogenous substance P induced an increase in histamine release (136 +/- 7%) which was significantly greater in lungs perfused with the neutral endopeptidase inhibitor, thiorphan (10(-5) M) (272 +/- 35%). This effect was prevented by atropine (10(-6) M). Pretreatment of lungs with imetit (5 x 10(-8) M), a selective H3 receptor agonist, prevented the capsaicin-induced release of both mediators. Imetit also blocked the carbachol-induced release of substance P but not of histamine. Exogenous substance P-evoked histamine release was inhibited by imetit. Therefore, it can be concluded that substance P released through the action of capsaicin can activate cholinergic fibers, leading to cholinoceptor stimulation with subsequent activation of C-fibers and mast cells. While the presence of presynaptic H3 receptors modulating substance P-induced acetylcholine release was only surmised, the existence of modulating histamine H3 receptors on C-fibers was confirmed.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Nemmar, A.; Université de Liège - ULiège
Delaunois, Annie ; Université de Liège - ULiège > Relations académiques et scientifiques (Méd. vétérinaire)
Beckers, Jean-François ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie de la reproduction
Sulon, Joseph ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie de la reproduction
Bloden, Serge ; Université de Liège - ULiège > Département de sciences fonctionnelles > Département de sciences fonctionnelles
Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Language :
English
Title :
Modulatory Effect of Imetit, a Histamine H3 Receptor Agonist, on C-Fibers, Cholinergic Fibers and Mast Cells in Rabbit Lungs in Vitro
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