Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine
Abstract The nematode parasite intestine absorbs nutrients, is involved in innate immunity, can metabolize xenobiotics and as we show here, is also a site of action of the anthelmintic, diethylcarbamazine. Diethylcarbamazine (DEC) is used to treat lymphatic filariasis and activates TRP-2, GON-2 &...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-25648-7 |
| _version_ | 1828170114528182272 |
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| author | Paul D. E. Williams Sudhanva S. Kashyap Mark A. McHugh Matthew T. Brewer Alan P. Robertson Richard J. Martin |
| author_facet | Paul D. E. Williams Sudhanva S. Kashyap Mark A. McHugh Matthew T. Brewer Alan P. Robertson Richard J. Martin |
| author_sort | Paul D. E. Williams |
| collection | DOAJ |
| description | Abstract The nematode parasite intestine absorbs nutrients, is involved in innate immunity, can metabolize xenobiotics and as we show here, is also a site of action of the anthelmintic, diethylcarbamazine. Diethylcarbamazine (DEC) is used to treat lymphatic filariasis and activates TRP-2, GON-2 & CED-11 TRP channels in Brugia malayi muscle cells producing spastic paralysis. DEC also has stimulatory effects on ascarid nematode parasites. Using PCR techniques, we detected, in Ascaris suum intestine, message for: Asu-trp-2, Asu-gon-2, Asu-ced-11, Asu-ocr-1, Asu-osm-9 and Asu-trpa-1. Comparison of amino-acid sequences of the TRP channels of B. malayi, and A. suum revealed noteworthy similarity, suggesting that the intestine of Ascaris will also be sensitive to DEC. We used Fluo-3AM as a Ca2+ indicator and observed characteristic unsteady time-dependent increases in the Ca2+ signal in the intestine in response to DEC. Application of La3+ and the TRP channel inhibitors, 2-APB or SKF 96365, inhibited DEC mediated increases in intracellular Ca2+. These observations are important because they emphasize that the nematode intestine, in addition to muscle, is a site of action of DEC as well as other anthelmintics. DEC may also enhance the Ca2+ toxicity effects of other anthelmintics acting on the intestine or, increase the effects of other anthelmintics that are metabolized and excreted by the nematode intestine. |
| first_indexed | 2024-04-12T03:03:23Z |
| format | Article |
| id | doaj.art-f34fb595600a4b6e90aa8629453e22eb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T03:03:23Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f34fb595600a4b6e90aa8629453e22eb2022-12-22T03:50:36ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-25648-7Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestinePaul D. E. Williams0Sudhanva S. Kashyap1Mark A. McHugh2Matthew T. Brewer3Alan P. Robertson4Richard J. Martin5Department of Biomedical Sciences, Iowa State UniversityDepartment of Biomedical Sciences, Iowa State UniversityDepartment of Biomedical Sciences, Iowa State UniversityDepartment of Veterinary Pathology, Iowa State UniversityDepartment of Biomedical Sciences, Iowa State UniversityDepartment of Biomedical Sciences, Iowa State UniversityAbstract The nematode parasite intestine absorbs nutrients, is involved in innate immunity, can metabolize xenobiotics and as we show here, is also a site of action of the anthelmintic, diethylcarbamazine. Diethylcarbamazine (DEC) is used to treat lymphatic filariasis and activates TRP-2, GON-2 & CED-11 TRP channels in Brugia malayi muscle cells producing spastic paralysis. DEC also has stimulatory effects on ascarid nematode parasites. Using PCR techniques, we detected, in Ascaris suum intestine, message for: Asu-trp-2, Asu-gon-2, Asu-ced-11, Asu-ocr-1, Asu-osm-9 and Asu-trpa-1. Comparison of amino-acid sequences of the TRP channels of B. malayi, and A. suum revealed noteworthy similarity, suggesting that the intestine of Ascaris will also be sensitive to DEC. We used Fluo-3AM as a Ca2+ indicator and observed characteristic unsteady time-dependent increases in the Ca2+ signal in the intestine in response to DEC. Application of La3+ and the TRP channel inhibitors, 2-APB or SKF 96365, inhibited DEC mediated increases in intracellular Ca2+. These observations are important because they emphasize that the nematode intestine, in addition to muscle, is a site of action of DEC as well as other anthelmintics. DEC may also enhance the Ca2+ toxicity effects of other anthelmintics acting on the intestine or, increase the effects of other anthelmintics that are metabolized and excreted by the nematode intestine.https://doi.org/10.1038/s41598-022-25648-7 |
| spellingShingle | Paul D. E. Williams Sudhanva S. Kashyap Mark A. McHugh Matthew T. Brewer Alan P. Robertson Richard J. Martin Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine Scientific Reports |
| title | Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine |
| title_full | Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine |
| title_fullStr | Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine |
| title_full_unstemmed | Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine |
| title_short | Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine |
| title_sort | diethylcarbamazine trp channels and ca2 signaling in cells of the ascaris intestine |
| url | https://doi.org/10.1038/s41598-022-25648-7 |
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