Inhibitory effect of anti-allergic drugs on cholinergic and non-cholinergic neurotransmissions of guinea pig bronchial muscle in vitro.
To determine whether anti-allergic drugs can inhibit autonomic neurotransmission of airway smooth muscle, we studied the effect of sodium cromoglycate (SCG, Intal) and related anti-allergic drugs on electrically induced neurogenic contractions of isolated guinea pig bronchial muscle. Electrical field stimulation (8 Hz, 0.5 msec, 30 V) evoked a biphasic contraction of bronchial muscle, consisting of an initial phasic component followed by a sustained one which was mediated by cholinergic and non-cholinergic nerve stimulations, respectively. Sodium cromoglycate, tranilast, ketotifen, and azelastine at concentrations higher than 10(-6) M caused a concentration-dependent inhibition in the height of the non-cholinergically mediated contractions. The cholinergically mediated contractions were also inhibited by tranilast, ketotifen, and azelastine but not by SCG. Submaximal contractions of bronchial muscle evoked by exogenous substance P (2 X 10(-7) M) were less potently inhibited by these drugs than those by exogenous acetylcholine (2 X 10(-6) M). These results indicate that in isolated guinea pig bronchial muscle, anti-allergic drugs may inhibit non-cholinergic neurotransmission mainly by prejunctional reduction of the transmitter release and partly by postjunctional depression of the response.
Kamikawa
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Department of Pharmacology, Dokkyo University School of Medicine, Tochigi, Japan.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation*; D002799:Cholinergic Fibers / Q000187:drug effects*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D010793:Phthalazines / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D062367:ortho-Aminobenzoates; C012293:tranilast; D000109:Acetylcholine; D004205:Cromolyn Sodium; D007665:Ketotifen; C020976:azelastine