Allergic responses and subsequent development of airway hyperreactivity to cold provocation in the rat trachea: pharmacological modulation.
An in vitro model of airway hyperreactivity to cold provocation was developed. Cold provocation (10 degrees C) alone was not sufficient to cause contraction of rat isolated tracheal smooth muscle preparations. However, following recovery from antigen-induced responses in sensitized rat tracheal segments, cold provocation resulted in marked contractile responses. L-652,731 (a Paf-acether antagonist) and atropine significantly attenuated antigen-induced responses and subsequent development of airway hyperreactivity to cold provocation. Indomethacin augmented allergic responses and subsequent development of airway hyperreactivity to cold challenge. Nordihydroguaiaretic acid, FPL 55712 and theophylline did not exert any effect. The data obtained in this study showed that (i) Paf-acether and acetylcholine may play an important role in the mediation of allergic responses and subsequent development of airway hyperreactivity to cold provocation; (ii) the significant attenuation of antigen-induced airway hyperreactivity to cold provocation by Ca2+ channel blockers (nifedipine, bepridil and TMB-8) suggests an increase in Ca2+ influx/permeability following antigen challenge which appears to be responsible for the development of airway hyperreactivity to cold provocation; and (iii) 5-HT, prostaglandins or thromboxanes and leukotrienes play little or no role in the mediation of allergic responses and subsequent development of airway hyperreactivity to cold exposure in rat trachea.
Chand
N
N
Wallace Laboratories, Division of Carter-Wallace, Inc., Cranbury, NJ 08512.
Diamantis
W
W
Mahoney
T P
TP
Sofia
R D
RD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D003080:Cold Temperature; D066298:In Vitro Techniques; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002147:Calmodulin; D010276:Parasympatholytics; D012702:Serotonin Antagonists; D010047:Ovalbumin; D000109:Acetylcholine