Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole
Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that t...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Hill, K. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2004 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag 2004 |
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| Übergeordnetes Werk: |
Enthalten in: Naunyn-Schmiedeberg's archives of pharmacology - Berlin : Springer, 1873, 370(2004), 4 vom: 30. Sept., Seite 227-237 |
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| Übergeordnetes Werk: |
volume:370 ; year:2004 ; number:4 ; day:30 ; month:09 ; pages:227-237 |
| Links: |
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| DOI / URN: |
10.1007/s00210-004-0981-y |
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| Katalog-ID: |
SPR001949128 |
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| 100 | 1 | |a Hill, K. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole |
| 264 | 1 | |c 2004 | |
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| 520 | |a Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. | ||
| 650 | 4 | |a Transient Receptor Potential |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Clotrimazole |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Transient Receptor Potential Channel |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Econazole |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a TRPM2 Channel |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a McNulty, S. |4 aut | |
| 700 | 1 | |a Randall, A. D. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Naunyn-Schmiedeberg's archives of pharmacology |d Berlin : Springer, 1873 |g 370(2004), 4 vom: 30. Sept., Seite 227-237 |w (DE-627)254638309 |w (DE-600)1462940-9 |x 1432-1912 |7 nnns |
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2004 |
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2004 |
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10.1007/s00210-004-0981-y doi (DE-627)SPR001949128 (SPR)s00210-004-0981-y-e DE-627 ger DE-627 rakwb eng Hill, K. verfasserin aut Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2004 Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. Transient Receptor Potential (dpeaa)DE-He213 Clotrimazole (dpeaa)DE-He213 Transient Receptor Potential Channel (dpeaa)DE-He213 Econazole (dpeaa)DE-He213 TRPM2 Channel (dpeaa)DE-He213 McNulty, S. aut Randall, A. D. aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 370(2004), 4 vom: 30. Sept., Seite 227-237 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:370 year:2004 number:4 day:30 month:09 pages:227-237 https://dx.doi.org/10.1007/s00210-004-0981-y lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 370 2004 4 30 09 227-237 |
| spelling |
10.1007/s00210-004-0981-y doi (DE-627)SPR001949128 (SPR)s00210-004-0981-y-e DE-627 ger DE-627 rakwb eng Hill, K. verfasserin aut Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2004 Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. Transient Receptor Potential (dpeaa)DE-He213 Clotrimazole (dpeaa)DE-He213 Transient Receptor Potential Channel (dpeaa)DE-He213 Econazole (dpeaa)DE-He213 TRPM2 Channel (dpeaa)DE-He213 McNulty, S. aut Randall, A. D. aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 370(2004), 4 vom: 30. Sept., Seite 227-237 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:370 year:2004 number:4 day:30 month:09 pages:227-237 https://dx.doi.org/10.1007/s00210-004-0981-y lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 370 2004 4 30 09 227-237 |
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10.1007/s00210-004-0981-y doi (DE-627)SPR001949128 (SPR)s00210-004-0981-y-e DE-627 ger DE-627 rakwb eng Hill, K. verfasserin aut Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2004 Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. Transient Receptor Potential (dpeaa)DE-He213 Clotrimazole (dpeaa)DE-He213 Transient Receptor Potential Channel (dpeaa)DE-He213 Econazole (dpeaa)DE-He213 TRPM2 Channel (dpeaa)DE-He213 McNulty, S. aut Randall, A. D. aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 370(2004), 4 vom: 30. Sept., Seite 227-237 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:370 year:2004 number:4 day:30 month:09 pages:227-237 https://dx.doi.org/10.1007/s00210-004-0981-y lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 370 2004 4 30 09 227-237 |
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10.1007/s00210-004-0981-y doi (DE-627)SPR001949128 (SPR)s00210-004-0981-y-e DE-627 ger DE-627 rakwb eng Hill, K. verfasserin aut Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2004 Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. Transient Receptor Potential (dpeaa)DE-He213 Clotrimazole (dpeaa)DE-He213 Transient Receptor Potential Channel (dpeaa)DE-He213 Econazole (dpeaa)DE-He213 TRPM2 Channel (dpeaa)DE-He213 McNulty, S. aut Randall, A. D. aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 370(2004), 4 vom: 30. Sept., Seite 227-237 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:370 year:2004 number:4 day:30 month:09 pages:227-237 https://dx.doi.org/10.1007/s00210-004-0981-y lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 370 2004 4 30 09 227-237 |
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10.1007/s00210-004-0981-y doi (DE-627)SPR001949128 (SPR)s00210-004-0981-y-e DE-627 ger DE-627 rakwb eng Hill, K. verfasserin aut Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2004 Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. Transient Receptor Potential (dpeaa)DE-He213 Clotrimazole (dpeaa)DE-He213 Transient Receptor Potential Channel (dpeaa)DE-He213 Econazole (dpeaa)DE-He213 TRPM2 Channel (dpeaa)DE-He213 McNulty, S. aut Randall, A. D. aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 370(2004), 4 vom: 30. Sept., Seite 227-237 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:370 year:2004 number:4 day:30 month:09 pages:227-237 https://dx.doi.org/10.1007/s00210-004-0981-y lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 370 2004 4 30 09 227-237 |
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Enthalten in Naunyn-Schmiedeberg's archives of pharmacology 370(2004), 4 vom: 30. Sept., Seite 227-237 volume:370 year:2004 number:4 day:30 month:09 pages:227-237 |
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To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. 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| author |
Hill, K. |
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Hill, K. misc Transient Receptor Potential misc Clotrimazole misc Transient Receptor Potential Channel misc Econazole misc TRPM2 Channel Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole |
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Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole Transient Receptor Potential (dpeaa)DE-He213 Clotrimazole (dpeaa)DE-He213 Transient Receptor Potential Channel (dpeaa)DE-He213 Econazole (dpeaa)DE-He213 TRPM2 Channel (dpeaa)DE-He213 |
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Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole |
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inhibition of trpm2 channels by the antifungal agents clotrimazole and econazole |
| title_auth |
Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole |
| abstract |
Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. © Springer-Verlag 2004 |
| abstractGer |
Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. © Springer-Verlag 2004 |
| abstract_unstemmed |
Abstract TRPM2 is a $ Ca^{2+} $-permeable non-selective cation channel that uniquely is activated by intracellular ADP-ribose. To date, only one pharmacological blocker of this channel, namely flufenamic acid (FFA), has been described. Here we demonstrate, using patch clamp electrophysiology, that the antifungal imidazoles clotrimazole and econazole inhibit ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). For both compounds, all concentrations in a range from 3 μM to 30 μM produced an essentially complete inhibition of the TRPM2-mediated current. The rate of current antagonism was dependent on the concentration applied, with higher concentrations producing faster block. In addition, decreasing extracellular pH accelerated inhibition of TRPM2 by both clotrimazole and econazole; extracellular alkalisation produced the converse effect. Additional experiments indicated hTRPM2 activation was required for the antagonism of either compound to develop, and that neither compound blocked from the intracellular face of the plasma membrane. ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1 were also antagonised by clotrimazole. Contrary to the observations made with hTRPM2, antagonism in CRI-G1 cells could be largely reversed following clotrimazole removal. These experiments suggest that imidazole antifungals may be useful tool antagonists for future studies of TRPM2 function. © Springer-Verlag 2004 |
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Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole |
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https://dx.doi.org/10.1007/s00210-004-0981-y |
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McNulty, S. Randall, A. D. |
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10.1007/s00210-004-0981-y |
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| score |
7.402135 |