Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum.

摘要: The mycotoxin, cyclopiazonic acid (CPA), inhibits the Ca2+-stimulated ATPase (EC 3.6.1.38) and Ca2+ transport activity of sarcoplasmic reticulum (Goeger, D. E., Riley, R. T., Dorner, J. W., Cole, (1988) Biochem. Pharmacol. 37, 978-981). We found that at low ATP concentrations (0.5-2 microM) inhibition was essentially complete a CPA concentration 6-8 nmol/mg protein, indicating stoichiometric reaction with Ca2+-ATPase. Cyclopiazonic caused similar hydrolysis in intact purified preparation also inhibited Ca2+-dependent acetylphosphate, p-nitrophenylphosphate carbamylphosphate by reticulum. protected enzyme competitive manner against CPA, while 10(5)-fold change free had only moderate effect on extent inhibition. did not influence crystallization Ca2+-ATPase vanadate or fluorescein-5'-isothiocyanate Ca2+-ATPase, but it completely blocked as 1-2 mol CPA/mol fluorescence changes induced [ethylenebis(oxyethylenenitrilo)]tetraacetic (EGTA) FITC-labeled cleavage trypsin T2 site presence EGTA. These observations suggest interferes ATP-induced conformational related to transport. appears be fairly specific, since kidney brain Na+,K+-ATPase 3.6.1.37), gastric H+,K+-ATPase 3.6.1.36), mitochondrial F1-ATPase 3.6.1.34), erythrocytes, Mg2+-activated T-tubules surface membranes rat skeletal muscle were even high 1000 protein.