Effect of calcium antagonists on the biosynthesis and contractile effects of peptidoleukotrienes in rhesus monkey lung.
Anti-human Ig (immunoglobulin) E induced the release of 2.84 +/- 0.33 ng/ml of immunoreactive leukotrienes (iLTs) from passively sensitized, fragmented rhesus monkey lung, whereas tissue not challenged with anti-IgE released 0.21 +/- 0.08 ng/ml of iLTs spontaneously. Whereas the preferential lipoxygenase inhibitor, nordihydroguaiaretic acid (100 microM), inhibited completely anti-IgE-induced release of iLTs, the calcium channel entry blockers, nifedipine and verapamil (1 and 10 microM), and the purported intracellular calcium antagonist, TMB-8 (100 microM), were without affect on iLT release. The cyclooxygenase inhibitor, indomethacin (5 microM), potentiated iLT release by an average 27.7%. Anti-IgE also induced a contraction of the sensitized monkey lung parenchyma, which was partially suppressed by the antihistamine, mepyramine (10 microM). Against the residual contraction elicited by anti-IgE in the presence of mepyramine, neither FPL 55712 (10 microM) nor verapamil (10 microM) significantly suppressed the contractile activity of anti-IgE. On the monkey lung parenchyma, LTD4 elicited a concentration-dependent contraction, which was antagonized by FPL 55712 (KB = 1 microM) and suppressed by 40 to 50% by verapamil (10 microM). On monkey tracheal rings, the contraction elicited by LTD4 (30 nM) was suppressed by an average 83% by FPL 55712 (10 microM), 47% by verapamil (1 microM) and 45% by TMB-8 (100 microM). In contrast, the KCI-induced contraction was suppressed completely by verapamil and suppressed 79% by TMB-8, suggesting that LTD4 does not elicit contraction of the monkey trachea simply via voltage sensitive calcium entry.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002867:Chromones / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D013189:SRS-A / Q000096:biosynthesis* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002867:Chromones; D013189:SRS-A; D007073:Immunoglobulin E; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C006312:FPL 55712; D014700:Verapamil; D009543:Nifedipine