IS THE PHOSPHOLIPASE A(2) PATHWAY IMPLICATED IN SARCOLEMMA DAMAGE OF THE RAT-HEART

The Langendorff-perfused rat heart has been used to test the hypothesi s that Ca2+-activation of the phospholipase A(2) (PLA(2)) is implicate d in the damage of the sarcolemma. Creatine kinase (CK) efflux was mon itored following a standard Ca2+-paradox or treatment with 10 mM caffe ine or 1 mM 2,4-dinitrophenol. Mepacrine (PLA(2) inhibitor) or nordihy droguaretic acid (NDGA, lipoxygenase inhibitor) did not protect agains t CK release in the standard Ca2+-paradox. Mepacrine, NDGA or phenidon e (lipoxygenase and cycloxygenase inhibitor) did not protect against m ild conditions of the Ca2+-paradox. No reduction in caffeine- or DNP-i nduced CK release was afforded by mepacrine. It is concluded that the PLA(2) cascade is stimulated by a rise in [Ca2+](1) but has no major r ole in CK release.