Effect of Triton X-100 on Tegument and Muscle in Schistosoma mansoni

Depenbusch, J W; Bricker, Connie S.; Bennett, James L.; Pax, Ralph A.

doi:10.2307/3281000

Cited by 6 publications

(2 citation statements)

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“…In addition to the role of antischistosome drugs as agents of tegumental disruption, a number of widely divergent compounds, not anthelmintic per se, also induce changes in the parasite tegument. Such substances include colchicine (Bogitsh & Carter, 1980), some lectins (Simpson & McLaren, 1982), detergents (Triton X-100) (Depenbusch, Bricker, Bennett & Pax, 1982) and hydrophobic compounds (pristane) (Kusel, Stones & Tetley, 1980). Information derived from the action of such compounds will be of considerable relevance in the design of novel drugs that target the parasite surface and additionally provides insights into the properties of the helminth tegument, how it varies developmentally and differs from host membranes.…”

Section: Anthelmintic Drugs Digeneamentioning

confidence: 99%

The interactions between drugs and the parasite surface

Chappell

1988

Parasitology

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SUMMARYThe interrelationships between drugs and parasite surfaces are considered under the headings of (a) effects on membrane transport, (b) drug uptake mechanisms and (c) effects on surface morphology and function: praziquantel is discussed under a separate heading. The range of chemotherapeutic compounds that cause permeability changes and concomitant morphological disruption is discussed in terms of mode of drug action. Interpretation of the available data renders it difficult to identify the primary mode of action in the drugs considered. Drug uptake mechanisms are known for relatively few compounds; drug resistance as a function of drug acquisition is discussed. The role of the parasite surface as a specific drug target is argued.

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Section: Anthelmintic Drugs Digeneamentioning

confidence: 99%

The interactions between drugs and the parasite surface

Chappell

1988

Parasitology

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“…The sarcolemma also possesses a praziquantelsensitive site. While the tegument appears to regulate extracellular Ca 2+ within the parasite, detegumented parasites are still responsive to praziquantel and 60 mM K + stimulation (Depenbusch et al 1982(Depenbusch et al , 1983 demonstrating that loss of the Ca 2+ influx site in the tegument does not alter muscle function or the muscle's sensitivity to praziquantel. Praziquantel still induces flaccid paralysis of detegumented worms in 30 mM Mg 2+ I-RPMI.…”

Section: Par 104mentioning

confidence: 99%

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

1992

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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 Mg(2+)-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 microM 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 Ca(2+)-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.

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Chlorpromazine, other amphiphilic cationic drugs and praziquantel: effects on carbohydrate metabolism ofSchistosoma mansoni

1987

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The effects of the amphiphilic cationic drugs chlorpromazine, imipramine, amitriptyline, propranolol and fluoxetine and praziquantel were investigated on glucose uptake and lactate excretion of Schistosoma mansoni. While praziquantel enhances glucose uptake and lactate excretion at a concentration of 10(-7) M, all the other drugs exert the same effects at concentrations above 10(-5) M. Generally, a constant molar ratio of 1:2 is found between glucose uptake and lactate excretion. Above 10(-5) M, praziquantel inhibits glucose uptake and lactate excretion. Similar effects are caused by amphiphilic cationic drugs at 10(-3) M. Pre-incubation of S. mansoni with 10(-5) M praziquantel completely abolish the stimulation of carbohydrate metabolism by serotonin and by 5 X 10(-5) M chlorpromazine or fluoxetine. The action of praziquantel on S. mansoni resembles that of amphiphilic cationic drugs with respect to their influence on carbohydrate metabolism. This, together with data obtained from electrophysiological and electron microscopic studies, provides evidence for the hypothesis that praziquantel exerts its effect by interacting with membrane structures.

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Effect of Triton X-100 on Tegument and Muscle in Schistosoma mansoni

Cited by 6 publications

References 10 publications

The interactions between drugs and the parasite surface

The interactions between drugs and the parasite surface

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

Chlorpromazine, other amphiphilic cationic drugs and praziquantel: effects on carbohydrate metabolism ofSchistosoma mansoni

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