Effect of Apafant on bronchial hyperresponsiveness and down-regulation of beta-adrenoceptors induced by endotoxin in guinea pigs.
Intraperitoneal injection of endotoxin resulted in bronchial hyperreactivity to histamine in guinea pigs. In addition, endotoxin (lipopolysaccharide, LPS) caused a decrease in the relaxation of the lung parenchymal strips induced by the beta-adrenoceptor agonist, isoproterenol (isoprenaline), and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Apafant (CAS 105219-56-5, WEB 2086) was effective in the prevention of endotoxin-induced changes, i.e., bronchial hyperreactivity to histamine, a decrease in the relaxation of lung parenchymal strips induced by isoproterenol and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Ketotifen and ozagrel also prevented the bronchial hyperresponsiveness and endotoxin-induced deterioration of the beta-adrenergic system. No remarkable effect was observed with cromolyn sodium and salbutamol in the bronchial hyperreactivity to histamine induced by endotoxin in guinea pigs. Cromolyn sodium also caused no influence on the down-regulation of beta-adrenoceptors.
Sugimoto
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mihara
T
T
Hayakawa
T
T
Nakayama
Y
Y
Kishida
H
H
Kamei
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001381:Azepines / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002307:Cardiography, Impedance; D015536:Down-Regulation / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001381:Azepines; D001993:Bronchodilator Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; D014230:Triazoles; C052518:WEB 2086; C044101:endotoxin, Escherichia coli; D006632:Histamine; D007545:Isoproterenol