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FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni

Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuro...

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Autores principales: Novozhilova, Ekaterina, Kimber, Michael J., Qian, Hai, McVeigh, Paul, Robertson, Alan P., Zamanian, Mostafa, Maule, Aaron G., Day, Tim A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919380/
https://www.ncbi.nlm.nih.gov/pubmed/20706630
http://dx.doi.org/10.1371/journal.pntd.0000790
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author Novozhilova, Ekaterina
Kimber, Michael J.
Qian, Hai
McVeigh, Paul
Robertson, Alan P.
Zamanian, Mostafa
Maule, Aaron G.
Day, Tim A.
author_facet Novozhilova, Ekaterina
Kimber, Michael J.
Qian, Hai
McVeigh, Paul
Robertson, Alan P.
Zamanian, Mostafa
Maule, Aaron G.
Day, Tim A.
author_sort Novozhilova, Ekaterina
collection PubMed
description Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca(2+) influx through sarcolemmal voltage operated Ca(2+) channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca(2+) influx through VOCC currents using a PKC-dependent pathway.
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spelling pubmed-29193802010-08-12 FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni Novozhilova, Ekaterina Kimber, Michael J. Qian, Hai McVeigh, Paul Robertson, Alan P. Zamanian, Mostafa Maule, Aaron G. Day, Tim A. PLoS Negl Trop Dis Research Article Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca(2+) influx through sarcolemmal voltage operated Ca(2+) channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca(2+) influx through VOCC currents using a PKC-dependent pathway. Public Library of Science 2010-08-10 /pmc/articles/PMC2919380/ /pubmed/20706630 http://dx.doi.org/10.1371/journal.pntd.0000790 Text en Novozhilova et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Novozhilova, Ekaterina
Kimber, Michael J.
Qian, Hai
McVeigh, Paul
Robertson, Alan P.
Zamanian, Mostafa
Maule, Aaron G.
Day, Tim A.
FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
title FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
title_full FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
title_fullStr FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
title_full_unstemmed FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
title_short FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
title_sort fmrfamide-like peptides (flps) enhance voltage-gated calcium currents to elicit muscle contraction in the human parasite schistosoma mansoni
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919380/
https://www.ncbi.nlm.nih.gov/pubmed/20706630
http://dx.doi.org/10.1371/journal.pntd.0000790
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