CYCLOPIAZONIC ACID

Description

Cyclopiazonic acid is a mycotoxin that has been found in Penicillium and Aspergillus and an inhibitor of sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA; IC₅₀ = 0.6 μM). In vivo, cyclopiazonic acid (11-14 mg/kg) induces ptosis, hypothermia, tremor, and cachexia, as well as induces lethality (LD₅₀ = 13 mg/kg), in rats. It induces tachycardia and sedation in rabbits when administered at a dose of 10 mg/kg.

Chemical Properties

off-white powder or crystals

Uses

The use of Cyclopiazonic acid on Langendorff-perfused murine hearts displayed anti-arrhythmic effects. Also, administration of cyclopiazonic acid on rat soleus muscle showed a decrease in hormone sensitive lipase activity and triacylglycerol hydrolysis. It is also used as an inhibitor of endoplasmic reticulum Ca2+-ATPase.

Uses

Cyclopiazonic acid is a tremorigenic indole produced by several species of Aspergillus and Penicillium. Cyclopiazonic acid is a highly specific inhibitor of calcium ATPase of sarcoplasmic reticulum, altering calcium homeostasis and ATP-dependent calcium transport and resulting in the release of intracellular stored Ca2+ without increasing IP3.

Uses

Cyclopiazonic acid fromPenicillium cyclopium has been used:

• as a standard in aflatoxin detection and quantification by thin layer chromatography (TLC)
• as a component in Ca²⁺-free DMEM/10% fetal bovine serum (FBS)
• as a reversible inhibitor of the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) to examine the role of luminal calcium in endoplasmic recticulum (ER)-to-Golgi trafficking
• as an endoplasmic reticulum Ca²⁺-ATPase blocker, to treat neurons and also to study the role of the endoplasmic reticulum (ER) in releasing and sustaining Ca²⁺during Ca²⁺-induced Ca²⁺ release (CICR) to inhibit SERCA

General Description

Cyclopiazonic acid (CPA), a tetramic acid is synthesized by various Aspergillus and Penicillium species.

Biological Activity

Cell-permeable, reversible inhibitor of sarcoplasmic reticulum Ca 2+ -ATPase.

Biochem/physiol Actions

Inhibits the sarcoplasmic reticulum Ca2+-pump.

storage

-20°C

References

[1] N W SEIDLER. Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum.[J]. The Journal of Biological Chemistry, 1989, 264 30: 17816-17823.
[2] Y UYAMA  M W  Y Imaizumi. Effects of cyclopiazonic acid, a novel Ca(2+)-ATPase inhibitor, on contractile responses in skinned ileal smooth muscle.[J]. British Journal of Pharmacology, 1992, 106 1: 208-214. DOI: 10.1111/j.1476-5381.1992.tb14316.x
[3] K. NISHIE  J. W D  R J Cole. Toxicity and neuropharmacology of cyclopiazonic acid[J]. Food and Chemical Toxicology, 1985, 23 9: Pages 831-839. DOI: 10.1016/0278-6915(85)90284-4