Contraction of the rat isolated aorta caused by Clostridium perfringens alpha toxin (phospholipase C): evidence for the involvement of arachidonic acid metabolism

Abstract

1 Alpha toxin produced by Clostridium perfringens contracted the rat isolated aorta and stimulated release of arachidonic acid in the tissue. 2 Quinacrine did not inhibit contraction caused by the toxin. 3 Indomethacin blocked contraction caused by the toxin in a dose-dependent manner and markedly increased levels of arachidonic acid released by the toxin. 4 The toxin-induced contraction was blocked by the thromboxane synthetase inhibitor OKY-046 and the thromboxane A₂ (TXA₂) antagonist ONO-3708. 5 The toxin stimulated production of TXB₂ and this was blocked by pretreatment with either indomethacin or OKY-046. 6 Toxin-induced contraction was diminished by pretreating aorta with collagenase or by rubbing the intimal surface to remove the endothelium. 7 These data suggest that the contractile response to the toxin is associated with stimulation of TXA₂ production from arachidonic acid released by the toxin in the endothelial cells of the aorta.