Porcine pancreatic phospholipase A 2-induced contractions of guinea pig lung pleural strips

Abstract

The contractile nature of porcine pancreatic phospholipase A 2 (PLA 2) was characterized on paired pleural strips obtained from guinea pig lung. PLA 2 (0.003–10 U/ml) produced concentration-related contractile responses which were sensitive to various drugs. The major component of the PLA 2-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 PLA 2-induced responses since 5-lipoxygenase inhibitors or the combination of a leukotriene (LT) B 4 receptor antagonist and an LTD 4/LTE 4 receptor antagonist only suppressed the maximal responses 22–32%. PLA 2-induced contractile responses were nearly abolished by altering both sides of the arachidonic acid cascade simultaneously. In contrast, a PAF receptor antagonist, a histamine (H 1) receptor antagonist and an acetylcholine receptor antagonist, failed to significantly reduce PLA 2-induced responses. These results demonstrate that exogenous administration of porcine pancreatic PLA 2 produced concentration-dependent contractions of pleural strips mediated through the generation of eicosanoids.