NEOMYCIN SELECTIVELY INHIBITS 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTIONIN THE GUINEA-PIG TRACHEA

Neomycin (3 mM) inhibited maximal 5-HT-induced contraction by approxim ately 50% without inhibiting [H-3]5-HT binding to 5-HT2A receptors. In contrast, neomycin had no effect on carbamylcholine- or histamine-ind uced contraction. Carbamylcholine (10 mu M) and histamine (10 mu M) bo th stimulated phosphatidylinositol (PI) hydrolysis but neomycin had no effect on the increase in PI hydrolysis. 5-HT (10 mu M) did not stimu late PI hydrolysis in the absence or presence of neomycin, suggesting that neomycin inhibited 5-HT contraction in the guinea pig trachea ind ependent of PI turnover. Although bradykinin stimulated phospholipase D (PLD) activity, 5-HT did not activate PLD, suggesting that the 5-HT2 A receptor is not coupled to this enzyme in the guinea pig trachea. Ne omycin (3 mM) and nitrendipine (1 mu M) inhibited 5-HT-induced contrac tion to a simliar extent, and neomycin did not further inhibit contrac tion in the presence of nitrendipine. These data indicate that neomyci n inhibited 5-HT-induced contraction, like nitrendipine, via an effect on calcium influx through L-type calcium channels and did not affect intracellular calcium release. However, unlike nitrendipine which comp letely blocked KCl-induced contraction, neomycin only marginally reduc ed the maximal KCl-induced contraction. Taken together, these data sug gest that neomycin may indirectly inhibit calcium influx through L-typ e calcium channels in guinea pig tracheal smooth muscle. The mechanism by which neomycin inhibited calcium influx in the guinea pig trachea may provide insight into the novel signaling pathway of the 5-HT2A rec eptor in this tissue.