Abstract

Kohn et al. [J. Biol. Chem. 276 (2001) 36873] demonstrated that cells expressing the structurally unusual schistosome β subunit SmCa_vβ1 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 SmCa_vβ1 and SmCa_vβ2 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 β 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 β subunits.

Author Keywords: Schistosoma mansoni; Praziquantel; Drug resistance; Calcium channels

Abbreviations: PZQ, praziquantel; B.I.D., beta interaction domain

Article Outline

1. Introduction

2. Materials and methods

2.1. Schistosomes

2.2. RNA, cDNA and sequencing

2.3. Northern blots

3. Results

4. Discussion

Acknowledgements

References

Corresponding author. Tel.: +39-06-90091357; fax: +39-06-90091259.

*1 Note: Nucleotide sequence data reported in this paper are available in the GenBank™, EMBL and DDBJ databases under the accession numbers: AY277530, AY277531, AY277532, AY277533, AY277534, AY277535, AY277536.