Effects of l‐serine borate on antagonism of leukotriene C4‐induced contractions of guinea‐pig trachea

Abstract

1 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 γ-glutamyltranspeptidase inhibitor, l-serine borate (SB). 2 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. 3 Salbutamol > isobutylmethylxanthine (IBMX) > dibutyryl cyclic AMP > aminophylline > 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. 4 Salbutamol and IBMX were potent functional antagonists of LTE₄-induced contractions both in the absence and presence of SB. 5 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.