Effects of epinastine hydrochloride on cholinergic neuro-effector transmission in canine tracheal smooth muscle.
We determined the effects of epinastine hydrochloride, an anti-asthmatic drug, on cholinergic neuro-effector transmission in canine trachea. Isometric tension of tracheal strips was measured in the presence of indomethacin and propranolol. Epinastine (10(-6) M) significantly suppressed the contraction evoked by electrical field stimulation, but had no effect on the acetylcholine-evoked contraction. An L-type Ca2+ channel blocker, nicardipine, did not suppress the electrical field stimulation-induced smooth muscle contraction and did not alter the inhibitory effect of epinastine. An N-type Ca2+ channel blocker, omega-conotoxin, suppressed the electrical field stimulation-induced contraction in a dose-dependent manner, and in a subthreshold/intermediate concentration abolished the inhibitory effect of epinastine. These findings indicate that epinastine exerts prejunctional inhibitory effects on airway smooth muscle of dogs, presumably by inhibiting acetylcholine release from vagal nerve terminals, and suggest that this effect is mediated by N-type Ca2+ channels.
Takahashi
N
N
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Aizawa
H
H
Inoue
H
H
Matsumoto
K
K
Nakano
H
H
Hirose
T
T
Nishima
S
S
Hara
N
N
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D003984:Dibenzazepines / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D018678:Cholinergic Agents; D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010455:Peptides; D014665:Vasodilator Agents; D020866:omega-Conotoxin GVIA; D009529:Nicardipine; C053090:epinastine