Hostname: page-component-848d4c4894-r5zm4 Total loading time: 0 Render date: 2024-07-06T05:46:50.335Z Has data issue: false hasContentIssue false
  • English
  • Français

Praziquantel: physiological evidence for its site(s) of action in magnesium-paralysed Schistosoma mansoni

Published online by Cambridge University Press:  06 April 2009

K. L. Blair ,
J. L. Bennett  and
R. A. Pax
K. L. Blair
Affiliation:
Department of Zoology and Neuroscience Program, Michigan State University, East Lansing, MI 48824–1115, USA
J. L. Bennett
Affiliation:
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824–1115, USA
R. A. Pax
Affiliation:
Department of Zoology and Neuroscience Program, Michigan State University, East Lansing, MI 48824–1115, USA
Get access Rights & Permissions [Opens in a new window]

Summary

The mechanism whereby praziquantel produces a contraction and subsequent flaccid paralysis (a loss of sensitivity to subsequent stimuli) of Schistosoma mansoni in a medium containing an elevated Mg2+:Ca2+ ratio was investigated. In RPMI, praziquantel produced a concentration-dependent tonic contraction of the parasite with an EC50 of 200 nM. Magnesium inhibited the contraction in such a manner as to convert the tonic contraction to a phasic one without altering the peak force generated. The Mg2+-dependent block was non-competitive with praziquantel but was competitive with extracellular Ca2+, ratios of 7·5:1; Mg2+: Ca2+ being needed to inhibit the tonic contraction and to induce flaccid paralysis. Flaccid paralysis was associated with a reduced ability of the parasite to take up 45Ca2+ from the bath compared to parasites that had not entered into flaccid paralysis and flaccid paralysis was reversible. Recovery from flaccid paralysis was accelerated by treatments that are expected to increase Ca2+ uptake by the parasite. At a concentration of 500 nM, praziquantel produced 2 distinct phasic contractions in intact parasites incubated in an elevated [Mg2+] medium but only 1 phasic contraction in parasites lacking their surface tegumental membranes. In zero Ca2+ I-RPMI, 10 μM praziquantel produced a phasic contraction of intact parasites but did not stimulate contraction of detegumented parasites until Ca2+ was reintroduced into the bath. These results indicate that praziquantel interacts with specific Ca2+-permeable sites in the tegumental and sarcoplasmic membranes of the parasite and that under these conditions of elevated Mg2+:Ca2+ ratios, these sites become blocked by Mg2+, leading to flaccid paralysis of the parasite.

Keywords

Schistosoma mansonimagnesiumpraziquantelmusclecalcium channelflatworm
Type
Research Article
Information
Parasitology , Volume 104 , Issue 1 , February 1992 , pp. 59 - 66
Copyright
Copyright © Cambridge University Press 1992

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Andrews, P. (1985). Praziquantel: mechanisms of antischistosomal activity. Pharmacological Therapeutics 29, 129–56.CrossRefGoogle Scholar
Bean, B. P. (1989). Classes of calcium channels in vertebrate cells. Annual Review of Physiology 51, 367–84.CrossRefGoogle ScholarPubMed
Blair, K. L. (1990). Phorbol ester-induced muscle contractions of Schistosoma mansoni. Ph.D. thesis, Michigan State University, East Lansing, Michigan, USA.Google Scholar
Bricker, C. S., Depenbusch, J. W., Bennett, J. L. & Thompson, D. P. (1983). The relationship between tegumental disruption and muscle contraction in Schistosome mansoni exposed to various compounds. Zeitschrift für Parasitenkunde 69, 61–71.CrossRefGoogle ScholarPubMed
Campbell, W. C. (1986). The chemotherapy of parasitic infections. Journal of Parasitology 72, 45–61.CrossRefGoogle ScholarPubMed
Chubb, J. M., Bennett, J. L., Akera, T. & Brody, T. M. (1978). Effects of praziquantel, a new antihelmintic, on electromechanical properties of isolated rat atria. Journal of Pharmacology and Experimental Therapeutics 207, 284–93.Google ScholarPubMed
Depenbusch, J. W., Bricker, C. S., Bennett, J. L. & Pax, R. A. (1982). Effect of Triton X-100 on tegument and muscle in Schistosoma mansoni. Journal of Parasitology 68, 884–91.CrossRefGoogle ScholarPubMed
Depenbusch, J. W., Thompson, D. P., Pax, R. A. & Bennett, J. L. (1983). Tegumental disruption with Triton X-100 and its effects on longitudinal muscle function in male Schistosoma mansoni. Parasitology 87, 61–73.CrossRefGoogle ScholarPubMed
Fetterer, R. H., Pax, R. A. & Bennett, J. L. (1977). Schistosoma mansoni: Direct method for simultaneous recording of electrical and motor activity. Experimental Parasitology 43, 286–94.CrossRefGoogle ScholarPubMed
Fetterer, R. H., Pax, R. A., Strand, S. & Bennett, J. L. (1978). Schistosoma mansoni: Physical and chemical factors affecting the mechanical properties of the adult male musculature. Experimental Parasitology 46, 59–71.CrossRefGoogle ScholarPubMed
Fetterer, R. H., Pax, R. A., Thompson, D., Bricker, C. & Bennett, J. L. (1980). Praziquantel: mode of its antischistosomal action. In The Host-Invader Interplay (ed. Van den Bossche, H.), pp. 695–8. Amsterdam: Elsevier, North Holland Biomedical Press.Google Scholar
Grider, J. R. & Makhlouf, G. M. (1988). Contraction mediated by Ca++ release in circular and Ca++ influx in longitudinal intestinal muscle cells. Journal of Pharmacology and Experimental Therapeutics 244, 432–7.Google ScholarPubMed
Harnett, W. (1988). The anthelmintic action of praziquantel. Parasitology Today 4, 144–6.CrossRefGoogle ScholarPubMed
Laduron, P. M. (1988). Stereospecificity in binding studies. Biochemical Pharmacology 37, 37–40.CrossRefGoogle ScholarPubMed
Lane, C. A., Pax, R. A. & Bennett, J. L. (1987). L-Glutamine: an amino acid required for maintenance of the tegumental membrane potential of Schistosoma mansoni. Parasitology 94, 233–42.CrossRefGoogle ScholarPubMed
Oaks, J. A., Cain, G. D., Mower, D. A. & Raj, R. K. (1981). Disruption and removal of the tegument from Schistosoma mansoni with Triton X-100. Journal of Parasitology 67, 711–65.CrossRefGoogle ScholarPubMed
Pax, R. A., Bennett, J. L. & Fetterer, R. (1978). A benzodiazepine derivative and praziquantel: Effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Nauyn-Schmiedeberg's Archives of Pharmacology 304, 309–15.CrossRefGoogle ScholarPubMed
Pax, R. A., Thompson, D. P. & Bennett, J. L. (1983). Action of praziquantel and the benzodiazepines on adult male Schistosoma mansoni. In Mechanism of Drug Action, (ed. Singer, T., Mansour, T. & Ondarza, R.), pp. 187–96. Orlando: Academic Press.Google Scholar
Thomas, H. & Andrews, P. (1977). Praziquantel – a new cestocide. Pesticide Science 8, 556–60.CrossRefGoogle Scholar
Thomas, H. & Gönnert, R. (1977). The efficacy of praziquantel against cestodes in animals. Zeitschrift für Parasitenkunde 52, 117–27.CrossRefGoogle ScholarPubMed
Thompson, D., Pax, R. A. & Bennett, J. L. (1982). Microelectrode studies of the tegument and subtegumental compartments of male Schistosoma mansoni: an analysis of electrophysiological properties. Parasitology 85, 163–78.CrossRefGoogle ScholarPubMed
Wolde Mussie, E., Vande Waa, J., Pax, R. A., Fetterer, R. & Bennett, J. L. (1982). Schistosoma mansoni: Calcium efflux and effects of calcium-free media on responses of the adult male musculature to praziquantel and other agents inducing contraction. Experimental Parasitology 53, 270–8.CrossRefGoogle ScholarPubMed
Xiao, S., Friedman, P. A., Catto, B. A. & Webster, L. T. (1984). Praziquantel-induced vesicle formation in the tegument of male Schistosoma mansoni is calcium dependent. Journal of Parasitology 70, 177–9.CrossRefGoogle ScholarPubMed
Xiao, S. & Catto, B. (1989). Comparative in vitro and in vivo activity of racemic praziquantel and its levorotated isomer on Schistosoma mansoni. Journal of Infectious Diseases 159, 589–92.Google ScholarPubMed