Contraction of the rat isolated aorta caused by Clostridium perfringens alpha toxin (phospholipase C): evidence for the involvement of arachidonic acid metabolism.
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.
Fujii
Y
Y
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Sakurai
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology*; D002135:Calcium-Binding Proteins; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D010738:Type C Phospholipases
D001095:Arachidonic Acids; D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D008689:Methacrylates; D016718:Arachidonic Acid; D013929:Thromboxane B2; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens; D013930:Thromboxane-A Synthase; C034364:ozagrel; D001241:Aspirin; D007213:Indomethacin