C5a and antigen-induced tracheal contraction: effect of a combination of an antihistamine and cyclo-oxygenase inhibitors.
Our previous studies with C5a, a cleavage product of the fifth component of complement, have shown that the antihistamine diphenhydramine and the cyclo-oxygenase inhibitor aspirin do not inhibit the C5a-induced contraction of isolated guinea pig trachea (Regal, Eastman & Pickering, 1980; Regal & Pickering, 1981). We investigated the effect of cyclo-oxygenase inhibitors in the presence of diphenhydramine to determine if cyclo-oxygenase products were contributing to the contraction beyond any effect they might have on histamine release. A combination of a cyclo-oxygenase inhibitor and diphenhydramine caused a delay in onset and decrease in magnitude and duration of the C5a-induced contraction. Indomethacin itself also caused a slight inhibition. In contrast, a combination of aspirin and diphenhydramine did not inhibit the initial portion of antigen-induced tracheal contraction any more than diphenhydramine alone and enhanced the later portion just as aspirin alone. Cross tachyphylaxis experiments demonstrated that antigen pretreatment significantly inhibited a subsequent C5a-induced tracheal contraction, though C5a pretreatment did not affect a subsequent antigen-induced contraction. Thus, cyclo-oxygenase products do contribute to C5a-induced tracheal contraction, and histamine participation in the presence of cyclo-oxygenase inhibitors is suggested. Our studies demonstrate the dissimilarities of C5a and antigen-induced contraction as regards inhibition by aspirin plus diphenhydramine, yet suggest common pathways leading to the contractile response as evidenced by cross tachyphylaxis experiments.
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001241:Aspirin / Q000494:pharmacology*; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a; D004155:Diphenhydramine / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth; D010105:Oxygenases / Q000037:antagonists & inhibitors; D013618:Tachyphylaxis; D014132:Trachea
D000941:Antigens; D003182:Complement C5; D000431:Ethanol; D015936:Complement C5a; D006632:Histamine; D004155:Diphenhydramine; D010105:Oxygenases; D001241:Aspirin; D007213:Indomethacin