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 -y-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 ofSB 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.

Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist

“…The interaction with LTC4 was similar to that observed with LTD4. However, in the presence of L-setine borate, contraction to LTC4 was not blocked by L-660,711, These findings are consistent with results obtained with previous LTB4 receptor antagonists (Snyder and &ell 1984;Jones et al 1986aJones et al , 1986Charette and Jones 1987) NrnPIC03.…”

Characterization of leukotriene-induced contraction of the guinea-pig gallbladder in vitro

“…In the presence of this antagonist, a higher csncentratisn sf LTC, ( > 10-%) was required to elicit an initial response. L-Serine borate, a y-glutamyltranspeptidase inhibitor, was used to prevent bisconversion of LTC4 to LTD4 (Charette and Jones 1987). Pretreatment with L-serine borate (45 mM) alone had a small yet significant ( p < 0.85) effect on gallbladder contraction but only at high LTC4 concentrations (Fig.…”

“…. L-Serine borate was prepared as previously described (Charette and Jones 1987). Nifedipine (Sigma Chemical Co., St. Louis, Mo.)…”

Dietary boron as a physiological regulator of the normal inflammatory response: A review and current research progress

“…An L-serine borate complex, 45 mM, reduced in vitro contractions induced by leukotriene LTC 4 in intralobar airways from human lung obtained after surgical resection [47]. Yet, L-serine borate unmasked contractile LTC 4 receptor mechanisms in isolated guinea-pig tracheal chains [48]. Because the leukotrienes are the major rate-limiting mediators of immuneinflammatory events in humans, boron may be in a key position to modulate the inflammatory process.…”