Endogenously formed leukotriene C4 activates LTC4 receptors in guinea pig tracheal strips

The bioconversion of leukotriene (LT) C4 to LTD4 via gamma-glutamyl transpeptidase is clearly defined in guinea pig trachea. Acivicin, an inhibitor of gamma-glutamyl transpeptidase, was used to study the contractile responses elicited by either endogenously released or exogenously administered LTC4 and the antagonistic nature of LY 171883 and ICI 204,219, LTD4/LTE4 receptor antagonists, on guinea pig tracheal strips. Pretreating tracheal strips with acivicin resulted in a concentration-related, selective leftward shift in the LTC4 concentration-response curves. Potency of LTC4 was increased 3-fold. Likewise, antigen concentration response curves were potentiated in acivicin-pretreated tissues. Antagonism of LTC4 and antigen contractile responses by LY 171883 and ICI 204,219 were reduced or abolished by acivicin-pretreatment. In contrast, these receptor antagonists effectively blocked LTD4 responses in control and acivicin-pretreated tissues. The results demonstrated that inhibition of gamma-glutamyl transpeptidase by acivicin blocked the bioconversion of LTC4 to LTD4 regardless of the source of LTC4. Data indicated that endogenously formed LTC4 was able to activate the LTC4 receptor in guinea pig tracheal strips.