Effects of a synthetic analog of polycavernoside A on human neuroblastoma cells.
BACKGROUND
Polycavernoside A is a glycosidic marine toxin first extracted from the red alga Polycavernosa tsudai in 1991 when 3 people died after the ingestion of this food. Polycavernoside A is an interesting molecule because of its complex macrolide structure and strong bioactivity. However, the target site of this toxin has not been characterized.


METHODS
We studied the effects of a synthethic analog of polycavernoside A on human neuroblastoma cells by measuring changes in membrane potential with bis-oxonol and variations in intracellular calcium levels with fura-2. Fluorescent phalloidin was utilized for assaying activity on actin cytoskeleton.


RESULTS
Data showed that this polycavernoside A analog induced a membrane depolarization and an increase in cytosolic calcium levels.


CONCLUSIONS
These results provide the first insight into the mode of action of polycavernoside A, suggesting that: i) this toxin triggers an initial extracellular calcium entry neither produced across L-type voltage-gated calcium channels nor activation of muscarinic receptors ii) there is a depolarization induced by the toxin and due to the extracellular calcium entry.
Cagide
Eva
E
Departamento de Farmacologia. Facultad de Veterinaria. Universidad de Santiago de Compostela. Campus de Lugo. Lugo, Spain.
Louzao
M Carmen
MC
Ares
Isabel R
IR
Vieytes
Mercedes R
MR
Yotsu-Yamashita
Mari
M
Paquette
Leo A
LA
Yasumoto
Takeshi
T
Botana
Luis M
LM
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002121:Calcium Channel Blockers; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004187:Disaccharides / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008564:Membrane Potentials; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy*; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D013997:Time Factors
D000199:Actins; D002121:Calcium Channel Blockers; D004187:Disaccharides; D018942:Macrolides; C121303:polycavernoside A; D009532:Nickel; D009543:Nifedipine; D002118:Calcium