Porcine pancreatic phospholipase A2-induced contractions of guinea pig lung pleural strips.
The contractile nature of porcine pancreatic phospholipase A2 (PLA2) was characterized on paired pleural strips obtained from guinea pig lung. PLA2 (0.003-10 U/ml) produced concentration-related contractile responses which were sensitive to various drugs. The major component of the PLA2-induced contractions was derived from products of the cyclooxygenase pathway since a cyclooxygenase inhibitor or the combination of a thromboxane synthetase inhibitor and a thromboxane receptor antagonist produced a 54-65% reduction of the contractile responses. 5-Lipoxygenase products contributed to a smaller component of the PLA2-induced responses since 5-lipoxygenase inhibitors or the combination of a leukotriene (LT) B4 receptor antagonist and an LTD4/LTE4 receptor antagonist only suppressed the maximal responses 22-32%. PLA2-induced contractile responses were nearly abolished by altering both sides of the arachidonic acid cascade simultaneously. In contrast, a PAF receptor antagonist, a histamine (H1) receptor antagonist and an acetylcholine receptor antagonist, failed to significantly reduce PLA2-induced responses. These results demonstrate that exogenous administration of porcine pancreatic PLA2 produced concentration-dependent contractions of pleural strips mediated through the generation of eicosanoids.
Sommers
C D
CD
Pulmonary Research, Eli Lilly and Company, Indianapolis, IN 46285.
Bobbitt
J L
JL
Bemis
K G
KG
Snyder
D W
DW
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism / Q000494:pharmacology*; D054467:Phospholipases A2; D010994:Pleura / Q000187:drug effects* / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2; D013930:Thromboxane-A Synthase; D007213:Indomethacin