Open AccessEffects of DS-4574, a New Orally Active Antiallergic Agent, in Experimental Allergic and Inflammatory Models
Author(s) -
Jun Tamaoki,
Atsushi Chiyotani,
Kiyoshi Takamatsu,
Toshinori Kanemura,
Naotaka Sakai,
Kunihiko Konno
Publication year - 1993
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.62.155
Subject(s) - histamine , arthus reaction , immunology , bronchoconstriction , immunoglobulin e , medicine , sensitization , ovalbumin , vascular permeability , allergy , edema , anaphylaxis , mast cell , inflammation , antibody , pharmacology , antigen , asthma
To determine the effects of the Kampo drugs Saiboku-to, Bakumondo-to and Orengedoku-to on beta-adrenergic function in airway smooth muscle, we studied isolated canine bronchial segments under isometric conditions in vitro. Incubation of tissues with these drugs did not alter the contractile responses to acetylcholine and histamine. The relaxation of tissues precontracted with acetylcholine induced by isoproterenol was augmented by Saiboku-to and Bakumondo-to, so that the concentration of isoproterenol required to produce a half-maximal effect (IC50) was decreased from 4.6 +/- 0.5 x 10(-8) M to 1.9 +/- 1.0 x 10(-8) M (P < 0.05) and to 1.0 +/- 0.8 x 10(-8) M (P < 0.01), respectively, whereas Orengedoku-to had no effect. These effects were concentration-dependent with the threshold concentrations being 0.3 mg/ml for Saiboku-to and 0.1 mg/ml for Bakumondo-to. Saiboku-to and Bakumondo-to did not affect cyclic AMP levels in airway smooth muscle per se but potentiated the isoproterenol-induced cyclic AMP accumulation. These results suggest that Saiboku-to and Bakumondo-to but not Orengedoku-to potentiate beta-adrenergic function in airway smooth muscle, which may reflect the efficacy of these drugs on airway hyperresponsiveness and asthma.