Sequence and level of endogenous expression of calcium channel beta subunits in Schistosoma mansoni displaying different susceptibilities to praziquantel.
Kohn et al. [J. Biol. Chem. 276 (2001) 36873] demonstrated that cells expressing the structurally unusual schistosome beta subunit SmCavbeta1 in their voltage-operated calcium channels, exhibit an increased current amplitude in the presence of praziquantel (PZQ). This suggests that the beta subunit is involved in PZQ activity and is consistent with the known pharmacological effects of the drug. If this is so, the low susceptibility to PZQ noted in some Schistosoma mansoni strains could be due to some mutation(s) in the gene coding for this protein. We have sequenced the cDNAs coding for the SmCavbeta1 and SmCavbeta2 subunits of different sensitive and resistant strains and we have not been able to detect any meaningful differences. As an alternative hypothesis, the different sensitivity of schistosomes to PZQ action could be due to the expression of different beta subunits in the parasite. This interpretation could also explain the low PZQ susceptibility of immature worms (28 days). We analyzed Northern blots of various strains and various developmental stages, but we were unable to demonstrate major quantitative differences in the expression of the beta subunits.
Valle
Cristiana
C
Institute of Cell Biology, C.N.R., 32 Via Ramarini, Monterotondo (RM), Italy. cvalle@ibc.cnr.it
Troiani
Anna Rita
AR
Festucci
Alfredo
A
Pica-Mattoccia
Livia
L
Liberti
Piero
P
Wolstenholme
Adrian
A
Francklow
Katherine
K
Doenhoff
Michael J
MJ
Cioli
Donato
D
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D004351:Drug Resistance; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D011223:Praziquantel / Q000494:pharmacology*; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016053:RNA, Protozoan / Q000737:chemistry / Q000302:isolation & purification; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D012556:Schistosomicides / Q000494:pharmacology*
D015220:Calcium Channels; D018076:DNA, Complementary; D021122:Protein Subunits; D016053:RNA, Protozoan; D012556:Schistosomicides; D011223:Praziquantel