Modulatory effect of imetit, a histamine H3 receptor agonist, on C-fibers, cholinergic fibers and mast cells in rabbit lungs in vitro

• Published in: European journal of pharmacology Vol. 371; no. 1; pp. 23 - 30
• Main Authors: NEMMAR, A, DELAUNOIS, A, BECKERS, J. F, SULON, J, BLODEN, S, GUSTIN, P
• Format: Journal Article Web Resource
• Language: English
• Published: Amsterdam Elsevier 23-04-1999; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Capsaicin - pharmacology; Carbachol - pharmacology; Cholinergic Fibers - drug effects; Cholinergic Fibers - metabolism; Drug Interactions; Female; Histamine Agonists - pharmacology; Histamine and antagonists. Allergy; Histamine Release - drug effects; Imidazoles - pharmacology; In Vitro Techniques; Life sciences; Lung - cytology; Lung - drug effects; Lung - metabolism; Male; Mast Cells - drug effects; Mast Cells - metabolism; Medical sciences; Médecine vétérinaire & santé animale; Pharmacology. Drug treatments; Rabbits; Radioimmunoassay; Receptors, Histamine H3 - drug effects; Sciences du vivant; Substance P - metabolism; Thiourea - analogs & derivatives; Thiourea - pharmacology; Veterinary medicine & animal health; Cholinergic neuron; Agonist; Substance P; Lung; Rabbit; Non adrenergic non cholinergic transmission; Molecular interaction; Lagomorpha; Respiratory system; In vitro; Nerve fiber C; Histamine; Vertebrata; Biological fixation; Mammalia; Animal; Mast cell; Mechanism of action; Release; H3 Histamine receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/s0014-2999(99)00176-4

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.