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STIMULATION OF ARACHIDONIC ACID METABOLISM AND GENERATION OF THROMBOXANE A 2 BY LEUKOTRIENES B 4 , C 4 AND D 4 IN GUINEA‐PIG LUNG in vitro
Author(s) -
PIPER PRISCILLA J.,
SAMHOUN MARWA N.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09295.x
Subject(s) - thromboxane a2 , leukotriene , arachidonic acid , bradykinin , leukotriene d4 , leukotriene c4 , phospholipase a2 , guinea pig , chemistry , thromboxane , prostaglandin , bronchoconstriction , medicine , mepacrine , endocrinology , phospholipase , tachyphylaxis , phospholipase a , biology , biochemistry , platelet , receptor , immunology , enzyme , asthma , malaria
1 Leukotriene C 4 (LTC 4 ), LTD 4 , slow‐reacting substance of anaphylaxis (SRS‐A) (from guinea‐pig lung), bradykinin (Bk) and arachidonic acid (AA) release thromboxane A 2 (TxA 2 ) and prostaglandin‐like materials from guinea‐pig isolated perfused lungs. 2 Release of TxA 2 induced by LTC 4 and LTD 4 is inhibited by a thromboxane synthetase inhibitor, imidazole (2.9 m m ). 3 Mepacrine (200 μ m ), a phospholipase inhibitor, inhibits release of TxA 2 and prostaglandin‐like materials caused by SRS‐A and Bk but not that due to exogenous AA 4 Leukotrienes B 4 , C 4 and D 4 are approximately equipotent in inducing dose‐related contractions of guinea‐pig parenchymal strips (GPPs). 5 Leukotriene‐induced contractions of GPPs are greatly inhibited by imidazole (2.9 m m ), carbox‐yheptylimidazole (24 μ m ) and mepacrine (400 μ m ). 6 FPL 55712 (1.9 μ m ), the SRS‐A antagonist, blocks contractions of GPPs induced by LTC 4 and LTD 4 but not those due to LTB 4 or Bk. 7 Tachyphylaxis to LTB 4 occurs in GPPs but not to LTC 4 or LTD 4 . 8 These results suggest that in guinea‐pig lung in vitro , LTB 4 , LTC 4 and LTD 4 activate a phospholipase with subsequent generation of cyclo‐oxygenase products of which TxA 2 plays an important role.