Prevention of Ca(2+)-induced hepatocyte plasma membrane bleb formation by inhibitors of eicosanoid synthesis.
Isolated rat hepatocytes were incubated in the presence of Ca2+ ionophore A23187 to induce the formation of plasma membrane blebs which appear to be a consequence of toxic or ischaemic cell injury. When incubated in the presence of both A23187 and an inhibitor of phospholipase A2, bleb formation was limited to that observed in the absence of A23187. Inhibitors of cyclooxygenase or thromboxane synthetase had similar effects. Incubation of isolated hepatocytes with individual eicosanoids showed that thromboxane B2 caused the formation of many plasma membrane blebs, prostaglandin E2 fewer than thromboxane B2 but more than prostacyclin which did not enhance bleb formation. These observations support the idea that Ca(2+)-induced cell injury and death may be mediated via a Ca(2+)-activated phospholipase A2, arachidonic acid release and eicosanoid formation.
Horton
A A
AA
School of Biochemistry, University of Birmingham, U.K.
Wood
J M
JM
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D051381:Rats; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D000001:Calcimycin; D010741:Phospholipases A; D054467:Phospholipases A2; D013930:Thromboxane-A Synthase; D002118:Calcium