Schistosoma mansoni: lack of correlation between praziquantel-induced intra-worm calcium influx and parasite death.
The schistosomicidal activity of praziquantel (PZQ) is accompanied by a large influx of calcium into the worms, suggesting that this phenomenon could be the source of the observed muscular contraction, surface disruption and eventual death of the parasite. We have incubated live adult schistosomes in a medium containing radioactive calcium and we were able to confirm that PZQ does indeed stimulate calcium entry into the parasite. An even higher calcium uptake, however, occurred in schistosomes exposed to PZQ after pre-incubation with cytochalasin D, a condition that suppresses PZQ schistosomicidal effects and allows the complete survival of the parasites. The calcium blockers nicardipine and nifedipine also failed to prevent the calcium influx induced by PZQ. Similarly, a large calcium influx occurred in 28-day-old worms exposed to PZQ, in spite of the fact that these immature worms are largely insensitive to the schistosomicidal effects of the drug. Schistosomes incubated overnight with radioactive calcium and PZQ and then returned to normal medium, retained a calcium content higher than worms pre-incubated with cytochalasin D, but the difference could be a consequence--rather than a cause--of schistosomicidal effects. These results suggest that calcium accumulation by itself, at least as measured in whole parasites maintained in vitro, may not represent an exhaustive explanation for the schistosomicidal effects of PZQ.
Pica-Mattoccia
Livia
L
Institute of Cell Biology, National Research Council, 32 Via Ramarini, 00015 Monterotondo, Rome, Italy.
Orsini
Tiziana
T
Basso
Annalisa
A
Festucci
Alfredo
A
Liberti
Piero
P
Guidi
Alessandra
A
Marcatto-Maggi
Ana-Luiza
AL
Nobre-Santana
Sonia
S
Troiani
Anna-Rita
AR
Cioli
Donato
D
Valle
Cristiana
C
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D015638:Cytochalasin D / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000378:metabolism; D012556:Schistosomicides / Q000494:pharmacology; D002998:Clonazepam / Q000031:analogs & derivatives
D000871:Anthelmintics; D001570:Benzodiazepinones; D002118:Calcium; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D015638:Cytochalasin D; D009529:Nicardipine; D009543:Nifedipine; D019384:Nucleic Acid Synthesis Inhibitors; D011223:Praziquantel; D012556:Schistosomicides; C020602:meclonazepam; D002998:Clonazepam