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 i...
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| Veröffentlicht in: | Experimental parasitology 2008-07, Vol.119 (3), p.332-335 |
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| creator | Pica-Mattoccia, Livia Orsini, Tiziana Basso, Annalisa Festucci, Alfredo Liberti, Piero Guidi, Alessandra Marcatto-Maggi, Ana-Luiza Nobre-Santana, Sonia Troiani, Anna-Rita Cioli, Donato Valle, Cristiana |
| description | 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. |
| doi_str_mv | 10.1016/j.exppara.2008.03.012 |
| format | Article |
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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.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2008.03.012</identifier><identifier>PMID: 18456260</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Animals ; Anthelmintics - pharmacology ; Benzodiazepinones - pharmacology ; Biological and medical sciences ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Calcium influx ; Calcium Radioisotopes ; Cytochalasin D ; Cytochalasin D - pharmacology ; Drug mechanism ; Freshwater ; Fundamental and applied biological sciences. Psychology ; Immature schistosomes ; Kinetics ; Life cycle. Host-agent relationship. Pathogenesis ; Male ; Mice ; Nicardipine ; Nicardipine - pharmacology ; Nifedipine - pharmacology ; Nucleic Acid Synthesis Inhibitors - pharmacology ; Praziquantel ; Praziquantel - pharmacology ; Protozoa ; Schistosoma mansoni ; Schistosoma mansoni - drug effects ; Schistosoma mansoni - metabolism ; Schistosomicides - pharmacology ; Trematode</subject><ispartof>Experimental parasitology, 2008-07, Vol.119 (3), p.332-335</ispartof><rights>2008 Elsevier Inc.</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-ca37289342b83f065bc1fdb2131521de5be474f1ffefeb5c304df3abc100fe263</citedby><cites>FETCH-LOGICAL-c424t-ca37289342b83f065bc1fdb2131521de5be474f1ffefeb5c304df3abc100fe263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exppara.2008.03.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20414976$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18456260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pica-Mattoccia, Livia</creatorcontrib><creatorcontrib>Orsini, Tiziana</creatorcontrib><creatorcontrib>Basso, Annalisa</creatorcontrib><creatorcontrib>Festucci, Alfredo</creatorcontrib><creatorcontrib>Liberti, Piero</creatorcontrib><creatorcontrib>Guidi, Alessandra</creatorcontrib><creatorcontrib>Marcatto-Maggi, Ana-Luiza</creatorcontrib><creatorcontrib>Nobre-Santana, Sonia</creatorcontrib><creatorcontrib>Troiani, Anna-Rita</creatorcontrib><creatorcontrib>Cioli, Donato</creatorcontrib><creatorcontrib>Valle, Cristiana</creatorcontrib><title>Schistosoma mansoni: Lack of correlation between praziquantel-induced intra-worm calcium influx and parasite death</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>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.</description><subject>Animals</subject><subject>Anthelmintics - pharmacology</subject><subject>Benzodiazepinones - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium influx</subject><subject>Calcium Radioisotopes</subject><subject>Cytochalasin D</subject><subject>Cytochalasin D - pharmacology</subject><subject>Drug mechanism</subject><subject>Freshwater</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Immature schistosomes</subject><subject>Kinetics</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Male</subject><subject>Mice</subject><subject>Nicardipine</subject><subject>Nicardipine - pharmacology</subject><subject>Nifedipine - pharmacology</subject><subject>Nucleic Acid Synthesis Inhibitors - pharmacology</subject><subject>Praziquantel</subject><subject>Praziquantel - pharmacology</subject><subject>Protozoa</subject><subject>Schistosoma mansoni</subject><subject>Schistosoma mansoni - drug effects</subject><subject>Schistosoma mansoni - metabolism</subject><subject>Schistosomicides - pharmacology</subject><subject>Trematode</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhJ4B8gVvC-CPZhAuqKr6klTgAZ8txxqqXxE5thxZ-PV5tBMeeLI2eGc-8DyEvGdQMWPv2WOP9suioaw7Q1SBqYPwR2THooeJS9o_JDoDJSna9vCDPUjpCARmXT8kF62TT8hZ2JH4zNy7lkMKs6ax9Ct69owdtftJgqQkx4qSzC54OmO8QPV2i_uNuV-0zTpXz42pwpM7nqKu7EGdq9GTcOpeSndZ7qv1IT2sml5GOqPPNc_LE6inhi-29JD8-fvh-_bk6fP305frqUBnJZa6MFnve9ULyoRMW2mYwzI4DZ4I1nI3YDCj30jJr0eLQGAFytEIXCsAib8UleXOeu8Rwu2LKanbJ4DRpj2FNas9a1vc9PAjyErjsJC9gcwZNDClFtGqJbtbxt2KgTlbUUW1W1MmKAqGKldL3avtgHWYc_3dtGgrwegN0KvnZqL1x6R_HQTLZ708nvT9zWHL75TCqZBz6YsBFNFmNwT2wyl9tjLAw</recordid><startdate>20080701</startdate><enddate>20080701</enddate><creator>Pica-Mattoccia, Livia</creator><creator>Orsini, Tiziana</creator><creator>Basso, Annalisa</creator><creator>Festucci, Alfredo</creator><creator>Liberti, Piero</creator><creator>Guidi, Alessandra</creator><creator>Marcatto-Maggi, Ana-Luiza</creator><creator>Nobre-Santana, Sonia</creator><creator>Troiani, Anna-Rita</creator><creator>Cioli, Donato</creator><creator>Valle, Cristiana</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>7X8</scope></search><sort><creationdate>20080701</creationdate><title>Schistosoma mansoni: Lack of correlation between praziquantel-induced intra-worm calcium influx and parasite death</title><author>Pica-Mattoccia, Livia ; Orsini, Tiziana ; Basso, Annalisa ; Festucci, Alfredo ; Liberti, Piero ; Guidi, Alessandra ; Marcatto-Maggi, Ana-Luiza ; Nobre-Santana, Sonia ; Troiani, Anna-Rita ; Cioli, Donato ; Valle, Cristiana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-ca37289342b83f065bc1fdb2131521de5be474f1ffefeb5c304df3abc100fe263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Anthelmintics - pharmacology</topic><topic>Benzodiazepinones - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium influx</topic><topic>Calcium Radioisotopes</topic><topic>Cytochalasin D</topic><topic>Cytochalasin D - pharmacology</topic><topic>Drug mechanism</topic><topic>Freshwater</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Immature schistosomes</topic><topic>Kinetics</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Male</topic><topic>Mice</topic><topic>Nicardipine</topic><topic>Nicardipine - pharmacology</topic><topic>Nifedipine - pharmacology</topic><topic>Nucleic Acid Synthesis Inhibitors - pharmacology</topic><topic>Praziquantel</topic><topic>Praziquantel - pharmacology</topic><topic>Protozoa</topic><topic>Schistosoma mansoni</topic><topic>Schistosoma mansoni - drug effects</topic><topic>Schistosoma mansoni - metabolism</topic><topic>Schistosomicides - pharmacology</topic><topic>Trematode</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pica-Mattoccia, Livia</creatorcontrib><creatorcontrib>Orsini, Tiziana</creatorcontrib><creatorcontrib>Basso, Annalisa</creatorcontrib><creatorcontrib>Festucci, Alfredo</creatorcontrib><creatorcontrib>Liberti, Piero</creatorcontrib><creatorcontrib>Guidi, Alessandra</creatorcontrib><creatorcontrib>Marcatto-Maggi, Ana-Luiza</creatorcontrib><creatorcontrib>Nobre-Santana, Sonia</creatorcontrib><creatorcontrib>Troiani, Anna-Rita</creatorcontrib><creatorcontrib>Cioli, Donato</creatorcontrib><creatorcontrib>Valle, Cristiana</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pica-Mattoccia, Livia</au><au>Orsini, Tiziana</au><au>Basso, Annalisa</au><au>Festucci, Alfredo</au><au>Liberti, Piero</au><au>Guidi, Alessandra</au><au>Marcatto-Maggi, Ana-Luiza</au><au>Nobre-Santana, Sonia</au><au>Troiani, Anna-Rita</au><au>Cioli, Donato</au><au>Valle, Cristiana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Schistosoma mansoni: Lack of correlation between praziquantel-induced intra-worm calcium influx and parasite death</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2008-07-01</date><risdate>2008</risdate><volume>119</volume><issue>3</issue><spage>332</spage><epage>335</epage><pages>332-335</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>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.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>18456260</pmid><doi>10.1016/j.exppara.2008.03.012</doi><tpages>4</tpages></addata></record> |
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| ispartof | Experimental parasitology, 2008-07, Vol.119 (3), p.332-335 |
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| subjects | Animals Anthelmintics - pharmacology Benzodiazepinones - pharmacology Biological and medical sciences Calcium - metabolism Calcium Channel Blockers - pharmacology Calcium influx Calcium Radioisotopes Cytochalasin D Cytochalasin D - pharmacology Drug mechanism Freshwater Fundamental and applied biological sciences. Psychology Immature schistosomes Kinetics Life cycle. Host-agent relationship. Pathogenesis Male Mice Nicardipine Nicardipine - pharmacology Nifedipine - pharmacology Nucleic Acid Synthesis Inhibitors - pharmacology Praziquantel Praziquantel - pharmacology Protozoa Schistosoma mansoni Schistosoma mansoni - drug effects Schistosoma mansoni - metabolism Schistosomicides - pharmacology Trematode |
| title | Schistosoma mansoni: Lack of correlation between praziquantel-induced intra-worm calcium influx and parasite death |
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