Traditional oriental herbal medicine, Bakumondo-to, suppresses vagal neuro-effector transmission in guinea pig trachea.
OBJECTIVE
Bakumondo-to (Maimendong tang) is a traditional oriental herbal medicine that has been used as an antitussive agent. We previously demonstrated that Bakumondo-to attenuates airway hyperresponsiveness induced by ozone. However, the mechanism(s) responsible for this effect remains unclear. In the present study, we examined the mechanism whereby Bakumondo-to inhibits ozone-induced airway hyperresponsiveness. First, we examined the effect of Bakumondo-to on prostanoids production, which are key mediators to airway hyperresponsiveness after ozone exposure. Second, we studied its effects on the vagal neuroeffector transmission, because vagal nerve is likely to play an important role in airway hyperresponsiveness after ozone.


METHODS
We measured the effects of Bakumondo-to on the concentrations of prostanoids in bronchoalveolar lavage fluid before and after ozone. We evaluated the effects of Bakumondo-to on the contraction of guinea pig tracheal smooth muscle evoked by electrical field stimulation (EFS) or the exogenous application of acetylcholine (ACh). Isometric tension of tracheal strips was measured in the presence of indomethacin (10(-6) M) and of guanethidine (10(-6) M).


RESULTS
Ozone caused significant increase in prostaglandin E2 (PGE2) and thromboxane B2 (TXB2); however, Bakumondo-to did not affect the increase in these prostanoids. Bakumondo-to (0.01 mg/mL-1 mg/mL) significantly suppressed the contraction evoked by EFS, but did not affect the ACh-evoked contraction, indicating that Bakumondo-to suppressed tracheal smooth muscle contraction pre-junctionally.


CONCLUSIONS
These results suggest that the mechanism by which Bakumondo-to inhibits airway hyperresponsiveness depends on inhibiting the release of acetylcholine from vagal nerve terminals.
Aizawa
H
H
First Department of Internal Medicine, School of Medicine, Kurume University, Kurume, Japan. aizawa@med.kurume-u.ac.jp
Yoshida
M
M
Inoue
H
H
Hara
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004558:Electric Stimulation / Q000379:methods; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008518:Medicine, East Asian Traditional; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D009451:Neuroeffector Junction / Q000187:drug effects / Q000503:physiopathology; D010126:Ozone / Q000008:administration & dosage; D011453:Prostaglandins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology
D000996:Antitussive Agents; D004365:Drugs, Chinese Herbal; D011453:Prostaglandins; D014665:Vasodilator Agents; C083181:bakumondo-to; D010126:Ozone; D000109:Acetylcholine