Biochemical and pharmacological studies of the mechanism of action of tenebrosin-C, a cardiac stimulatory and haemolytic protein from the sea anemone, Actinia tenebrosa.
Tenebrosin-C is a protein of mol. wt 19,500 that displays potent cardiac stimulatory and haemolytic activities. Its haemolytic activity is inhibited by sphingomyelin but not phosphatidylcholine, and is not affected by Ca2+. The positive inotropic effect of tenebrosin-C on isolated guinea pig right atria is inhibited by the cyclooxygenase blockers indomethacin and aspirin, the lipoxygenase blocker and leukotriene antagonist RG5901, and the phospholipase A2 inhibitor mepacrine. This activity of tenebrosin-C therefore appears to be due to stimulation of the release of arachidonic acid and subsequent formation of prostaglandins and leukotrienes. Phospholipase A2-like activity was found with some tenebrosin-C preparations, but did not correlate with their positive inotropic or haemolytic activities and was too weak to account for either of these effects. Treatment of tenebrosin-C with various proteases in order to obtain active fragments showed that the protein is remarkably resistant to proteolysis.
Galettis
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School of Biochemistry, University of New South Wales, Kensington, Australia.
Norton
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D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003063:Cnidaria / Q000032:analysis*; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007447:Invertebrate Hormones / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010447:Peptide Hydrolases / Q000494:pharmacology; D010741:Phospholipases A / Q000032:analysis; D054467:Phospholipases A2; D012615:Sea Anemones / Q000032:analysis*
D001095:Arachidonic Acids; D002316:Cardiotonic Agents; D007447:Invertebrate Hormones; C065772:tenebrosin C; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D010447:Peptide Hydrolases; D001241:Aspirin; D007213:Indomethacin