title: Inhibitory effect of midaglizole on alpha adrenoceptor agonist-induced contractions of canine tracheal smooth muscle.
abstract: To determine why midaglizole is effective in some patients with severe asthma, we investigated the inhibitory effects of midaglizole, prazosin or yohimbine on the BHT 920-, phenylephrine-, or noradrenaline-induced contractions of canine tracheal smooth muscle. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M) and precontraction with serotonin (3 x 10(-7) M), the tracheal muscle showed contractile responses to the exogenous administration of both alpha 1 and alpha 2 adrenoceptor agonists. Every alpha antagonist inhibited these agonist-induced contractions. Inhibitory activity of midaglizole (10(-4) M) for the alpha agonists was BHT-920 greater than noradrenaline greater than or equal to phenylephrine, while that of prazosin (3 x 10(-6) M) was phenylephrine greater than noradrenaline greater than BHT-920. Moreover, yohimbine completely inhibited the contractions at the lower concentration of 3 x 10(-7) M than that of other two antagonists. Our findings demonstrate that midaglizole dose-dependently inhibits airway contractions induced by alpha adrenoceptor agonists.
authors.affiliation: College of Medical Care and Technology, Gunma University.
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshie
authors.forename: K
authors.initials: K
authors.lastname: Iizuka
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Aibara
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Ono
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C032368:midaglizole; D011224:Prazosin