The mucosa mediates tachyphylaxis to leukotrienes C4, D4 and E4 in guinea pig trachea

Effects of mucosal abrasion on tracheal smooth muscle leukotriene C4, D4 and E4 tachyphylaxis and on histamine contractions before and after four leukotriene exposures were studied. In intact tracheae, leukotriene C4 and E4 second exposure contractions were greater than first. Subsequent contractions showed tachyphylaxis. Leukotriene D4 contractions exhibited progressive tachyphylaxis. Mucosal abrasion potentiated initial leukotriene C4 and D contractions and eliminated leukotriene C4, D4 and E4 tachyphylaxis. Four leukotriene (10(-8) M) exposures reduced histamine (10(-4) M) responses in intact but not abraded preparations. Thus leukotriene C4, D4 and E4 release non-specific inhibitor(s) from tracheal mucosa.