Abstract
The influence of epithelial removal on the antihistaminic activity of azelastine in the guinea-pig isolated cervical trachea and main bronchus was examined. In both preparations with an intact epithelium, histamine produced a concentration-dependent contraction, but its potency (pD2) and contractiliy (Emax) were significantly higher in the main bronchus than in the cervical trachea. Epithelial removal from these preparations significantly increased the pD2 values in both tracheal and bronchial preparation, while the Emax value was significantly increased only in the cervical trachea. When these preparations were pretreated with azelastine (20 or 200 nM), concentration-response curves for histamine shifted downward, but were not influenced by the presence of an intact epithelium. Neither concentration of azelastine significantly modified the contractile responsiveness of tracheal and bronchial preparations to carbachol or neurokinin A. These results indicate that azelastine selectively antagonizes the histamine-induced contraction of the guinea-pig airway smooth muscles with or without an intact epithelium.
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References
D. McTavih and E. M. Sorkin,Azelastine, — A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs38, 778–800 (1989).
S. Katayama, N. Akimoto, H. Shionoya, T. Morimoto and Y. Katoh,Anti-allergic effect of azelastine hydrochloride on immediate type hypersensitivity reactions in vitro and in vivo. Arzneim. Forsch.31, 1196–1203 (1981).
H.-J. Zechel, N. Brock, D. Lenke and U. Achterrath-Tuckermann,Pharmacological and toxicological properties of azelastine, a novel antiallergic agent. Arzneim. Forsch.31, 1184–1193 (1981).
K. Taniguchi and K. Takanaka,Inhibitory effects of various drugs on phorbol myristate acetate and n-formylmethionyl leucyl phenylalanine induced O −2 production in polymorphonuclear leukocytes. Biochem. Pharmacol.33, 3165–3169 (1985).
N. Chand, J. Pillar, W. Diamantis and R. D. Sofia,Inhibition of IgE-mediated allergic histamine release from rat peritoneal mast cells by azelastine and selected antiallergic drugs. Agents Action16, 318–322 (1985).
N. Chand, W. Diamantis and R. D. Sofia,Aniagonism of histamine and leukotrienes by azeukotrienes by azelastine in isolated guinea pig ileum. Agents Actions19, 164–168 (1986).
U. Achterrath-Tuckermann, T. Simmet, W. Luck, I. Szelenyi and B. A. Peskar,Inhibition of cysteinyl-leukotriene production by azelastine and its biological significance. Agents Actions24, 217–223 (1988).
Y. Kamikawa,Inhibitory effect of anti-allergic drugs on cholinergic and non-cholinergic neurotransmissions of guinea pig bronchial muscle in vitro. Ann Allergy63, 59–63 (1989).
H. Aizawa, H. Inoue, N. Miyazaki, T. Ikeda, N. Shigematsu and Y. Ito,Effects of azelastine on vagal neuroeffector transmission in canine and human airway smooth muscle. J. Allergy Clin. Immunol.86, 171–176 (1990).
H.-K. Lee, J. Ohya, C. A. Doupnik and N. Sperelakis,Effects of azelastine on contraction of guinea pig tracheal smooth muscle. Eur. J. Pharmacol.187, 67–74 (1990).
S. Umeki,Effects of anti-allergic drugs on human neutrophil superoxide-generating NADPH oxidase. Biochem. Pharmacol.43, 1109–1117 (1992).
L. A. Laitinen, M. Heino, A. Laitinen, T. Kava and T. Haahtela,Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am. Rev. Respir. Dis.131, 599–606 (1985).
K. J. Morrison, Y. Gao and P. M. Vanhoutte,Epithelial modulation of airway smooth muscle. Am. J. Physiol.258, L254-L262 (1990).
D. Spina and C. P. Page,The pharmacology of the respiratory epithelium. Pharmacol. Res.26, 17–32 (1992).
N. A. Flavahan, L. L. Aarhus, T. J. Rimele and P. M. Vanhoutte,Respiratory epithelium inhibits bronchial smooth muscle tone. J. Appl. Physiol.58, 834–838 (1985).
R. G. Goldie, J. M. Papadimitriou, J. W. Paterson, P. J. Rigby, H. M. Self and D. Spina,Influence of the epithelium on responsiveness of guinea-pig isolated trachea to contractile and relaxant agonists. Br. J. Pharmacol.87, 5–14 (1986).
M. C. Holroyde,The influence of epithelium on the responsiveness of guinea-pig isolated trachea. Br. J. Pharmacol.87, 501–507 (1986).
G. Braunstein, C. Labat, S. Brunelleschi, J. Benveniste, J, Marsac and C. Brink,Evidence that the histamine sensitivity and resonsiveness of guinea-pig isolated trachea are modulated by epithelial prostaglandin E 2 production. Br. J. Pharmacol.95, 300–308 (1988).
J. Tamaoki, A. Chiyotani, N. Sakai, K. Takeyama and K. Konno,Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium. Thorax48, 542–546 (1993).
M. King, E. M. App, J. G. Zayas, O. Ramirez and B. K. Rubin,Effect of azelastine pretreatment on airway epithelial function in a canine model of asthma. Eur. Resp. J.10, 256S (1990).
Y. Kamikawa and Y. Shimo,Adenosine selectively inhibits noncholinergic transmission in guinea pig bronchi. J. Appl. Physiol. 66. 2084–2091 (1989).
T. Yamanaka, T. Shoji, M. Murakami and T.Igarashi,Effects of azelastine, a new antiallergic drug, on the gastrointestinal tract. Arzneim. Forsch.31, 1203–1206 (1981).
T. B. Casale,The interaction of azelastine with human lung histamine H 1,beta, and muscarinic receptor-binding sites. J. Allergy Clin. Immunol.83, 771–776 (1989).
E. R. McFadden,Pathogenesis of asthma. J. Allergy clin. Immunol.73, 413–424 (1984).
P. J. Barnes,Asthma as an axone reflex. The Lancet February 1, 242–244 (1986).
N. Chand, K. Nolan, W. Diamantis and R. D. Sofia,Inhibition of acute lung anaphylaxis by aerosolized azelastine in guinea pigs sensitized by three different procedures. Ann. Allergy58, 344–349 (1987).
E. G. Lindström, R. G. G. Andersson, G. Granerus and N. Grundström,Is the airway epithelium responsible for histamine metabolism in the trachea of guinea pigs? Agents Actions33, 170–172 (1991).
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Kamikawa, Y. Influence of epithelial removal on the antihistaminic activity of azelastine in the guinea-pig airway smooth muscles. Agents and Actions 40, 135–140 (1993). https://doi.org/10.1007/BF01984052
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DOI: https://doi.org/10.1007/BF01984052