Effects of L-serine borate on antagonism of leukotriene C4-induced contractions of guinea-pig trachea.
The antagonist activity of three leukotriene D4 (LTD4) receptor antagonists and a number of bronchodilators was determined against LTC4-induced contractions of guinea-pig isolated tracheal chains in the absence and presence of the gamma-glutamyltranspeptidase inhibitor, L-serine borate (SB). The LTD4 receptor antagonists FPL-55712, L-649,923 and L-648,051 effectively antagonized LTC4 responses in the absence of SB but were ineffective in the presence of 15 and/or 45 mM SB. Salbutamol greater than isobutylmethylxanthine (IBMX) greater than dibutyryl cyclic AMP greater than aminophylline greater than nifedipine antagonized contractions to LTC4 in the absence of SB. In contrast, in the presence of SB the antagonist activity of all of these agents except nifedipine was significantly reduced. The antagonist activity of the Ca2+ entry blocker, nifedipine, was similar in the absence and presence of SB. Salbutamol and IBMX were potent functional antagonists of LTE4-induced contractions both in the absence and presence of SB. These results are consistent with the hypothesis that there are contractile LTC4 receptor mechanisms in guinea-pig trachea which are unmasked by SB and are not blocked by LTD4 receptor antagonists and which are less effectively down modulated by cyclic AMP-dependent bronchodilators.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001881:Borates / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors*; D012694:Serine / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D001881:Borates; D013189:SRS-A; C040900:serine-borate complex; D012694:Serine; D003994:Bucladesine; D009543:Nifedipine; D000420:Albuterol; D015056:1-Methyl-3-isobutylxanthine