CONTRACTION OF GUINEA-PIG LUNG PARENCHYMA BY PANCREATIC TYPE PHOSPHOLIPASE-A(2) VIA ITS SPECIFIC BINDING-SITE

Porcine pancreatic group I phospholipase A2 (PLA2-I) induced contraction of guinea pig lung parenchyma in a concentration-dependent manner. Its EC50 value was similar to the K(d) value calculated from the specific binding of I-125-labeled porcine PLA2-I in the membrane fraction of guinea pig lung. Type-specific action of PLA2's and homologous desensitization strongly implicated the involvement of PLA2-I-specific sites in the activation process. Thromboxane A2 was found to be the main product from lung tissue by PLA2-I action and the contractile response by PLA2-I was specifically suppressed by thromboxane A2 receptor antagonists and cyclooxygenase inhibitor, but not by leukotriene receptor antagonist and H1 blocker. These findings indicate that PLA2-I-induced contractile response may depend on the secondarily produced thromboxane A2, thus providing a new aspect of PLA2-I from the pathophysiological standpoint.