Role of sodium in antigen-induced contraction of tracheal smooth muscle in dogs.
We examined the role of Na+ influx in the airway response to antigen (ragweed pollen extract) in sensitized dogs, using amiloride analogs to block Na(+)-dependent processes. In in vivo studies, respiratory resistance was measured in amiloride treated and untreated groups. The resistance increased by 9.3 cmH2O.L-1.sec in response to ragweed aerosol in the untreated group, but increased only by 5.2 cmH2O.L-1.sec in the treated group. In in vitro studies, isometric tension was measured in ragweed pollen sensitized tracheal strips. Tissues were treated with amiloride or its derivatives (50 microM) for specifically blocking Na+ channels (phenamil), Na(+)-H+ exchanger [5-(N-methyl-N-guanidinocarbonyl methyl)-amiloride] or Na(+)-Ca2+ exchanger [5-(4-chlorobenzyl)-2',4'-dimethylbenzamil]. In untreated strips, tension increased in response to ragweed by 1.9 +/- 0.5 mN/mg. The increase was reduced by phenamil (95.2 +/- 2.5%; P < 0.01) and amiloride (41.7 +/- 13.1%; P < 0.01), but not by the other two agents. Furthermore, phenamil also inhibited histamine-induced tension response and histamine-induced 22Na+ uptake of the muscle. We conclude that antigen-induced airway response is attenuated by blocking Na+ influx in smooth muscle.
Department of Pharmacology, University of Manitoba, Winnipeg, Canada.
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J
Yu
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Guia
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Mink
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Kepron
E J
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Cragoe
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Sharma
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Bose
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000494:pharmacology*; D016084:Bronchoconstriction; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D007073:Immunoglobulin E / Q000096:biosynthesis; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000503:physiopathology; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014132:Trachea / Q000502:physiology*
D000941:Antigens; D015222:Sodium Channels; D007073:Immunoglobulin E; D000584:Amiloride; D006632:Histamine; D012964:Sodium