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Phospholipase A 2 induced airway hyperreactivity to cooling and acetylcholine in rat trachea: pharmacological modulation
Author(s) -
Chand N.,
Diamantis W.,
Mahoney T.P.,
Sofia R.D.
Publication year - 1988
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.1476-5381.1988.tb11622.x
Subject(s) - medicine , endocrinology , antagonist , chemistry , phospholipase a2 , receptor antagonist , nordihydroguaiaretic acid , leukotriene d4 , pharmacology , arachidonic acid , biology , biochemistry , receptor , enzyme
1 Rat isolated tracheal smooth muscle preparations respond to phospholipase A 2 (PLA 2 ) and phospholipase C (PLC) with contractile responses of highly variable magnitudes. Rat tracheae exposed to PLA 2 or PLC for a period of 10–30 min, exhibit airway hyperreactivity (AH) to cooling (10°C), i.e., respond with strong contractile responses. Phospholipase D neither contracted rat tracheae nor induced AH to cooling. 2 PLA 2 ‐induced AH to cooling was dependent on the presence of extracellular Ca 2+ in the physiological solution. 3 Verapamil, azelastine, diltiazem and TMB‐8 (each 10 μ m ) significantly attenuated PLA 2 ‐induced AH. This effect was not shared by nifedipine (10 μ m ). 4 Bepridil (10 μ m ), a Ca 2+ and calmodulin antagonist, also significantly attenuated AH induced by PLA 2 . 5 Indomethacin (a cyclo‐oxygenase inhibitor), AA‐861 (a selective 5‐lipoxygenase inhibitor), FPL 55712 (a leukotriene receptor antagonist), methysergide (a 5‐hydroxytryptamine D‐receptor antagonist) and pyrilamine (a histamine H 1 ‐receptor antagonist) exerted little or no effect on PLA 2 ‐induced AH to cooling. 6 Atropine significantly attenuated PLA 2 ‐induced AH suggesting the participation of acetylcholine. 7 Nordihydroguaiaretic acid (an antioxidant; 5‐lipoxygenase inhibitor) and BW 755C (an antioxidant; a dual inhibitor of cyclo‐oxygenase and 5‐lipoxygenase) significantly attenuated PLA 2 ‐induced AH to cooling. 8 In conclusion, these data show that PLA 2 (an enzyme involved in the synthesis of Paf‐acether, prostaglandins, thromboxanes, leukotrienes, diacylglycerol, superoxide free radicals and lipid peroxides, etc.) induces AH to cooling and acetylcholine in rat trachea. The induction of AH to cooling is dependent on the presence of extracellular Ca 2+ and is significantly attenuated by verapamil, diltiazem, bepridil, atropine and azelastine (an antiallergic/antiasthmatic drug).