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Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells.
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , |
| In: | Proceedings of the National Academy of Sciences, 89, 1992, 9, S. 3825-3829 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Mackie, K Hille, B Mackie, K Hille, B |
|---|---|
| author |
Mackie, K Hille, B |
| spellingShingle |
Mackie, K Hille, B Proceedings of the National Academy of Sciences Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Multidisciplinary |
| author_sort |
mackie, k |
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Mackie, K Hille, B 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.89.9.3825 <jats:p>The psychoactive properties of Cannabis sativa and its major biologically active constituent, delta 9-tetrahydrocannabinol, have been known for years. The recent identification and cloning of a specific cannabinoid receptor suggest that cannabinoids mimic endogenous compounds affecting neural signals for mood, memory, movement, and pain. Using whole-cell voltage clamp and the cannabinomimetic aminoalkylindole WIN 55,212-2, we have found that cannabinoid receptor activation reduces the amplitude of voltage-gated calcium currents in the neuroblastoma-glioma cell line NG108-15. The inhibition is potent, being half-maximal at less than 10 nM, and reversible. The inactive enantiomer, WIN 55,212-3, does not reduce calcium currents even at 1 microM. Of the several types of calcium currents in NG108-15 cells, cannabinoids predominantly inhibit an omega-conotoxin-sensitive, high-voltage-activated calcium current. Inhibition was blocked by incubation with pertussis toxin but was not altered by prior treatment with hydrolysis-resistant cAMP analogues together with a phosphodiesterase inhibitor, suggesting that the transduction pathway between the cannabinoid receptor and calcium channel involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. However, the development of inhibition is considerably slower than a pharmacologically similar pathway used by an alpha 2-adrenergic receptor in these cells. Our results suggest that inhibition of N-type calcium channels, which could decrease excitability and neurotransmitter release, may underlie some of the psychoactive effects of cannabinoids.</jats:p> Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proceedings of the National Academy of Sciences |
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| title |
Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_unstemmed |
Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_full |
Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_fullStr |
Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_full_unstemmed |
Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_short |
Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_sort |
cannabinoids inhibit n-type calcium channels in neuroblastoma-glioma cells. |
| topic |
Multidisciplinary |
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http://dx.doi.org/10.1073/pnas.89.9.3825 |
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1992 |
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3825-3829 |
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<jats:p>The psychoactive properties of Cannabis sativa and its major biologically active constituent, delta 9-tetrahydrocannabinol, have been known for years. The recent identification and cloning of a specific cannabinoid receptor suggest that cannabinoids mimic endogenous compounds affecting neural signals for mood, memory, movement, and pain. Using whole-cell voltage clamp and the cannabinomimetic aminoalkylindole WIN 55,212-2, we have found that cannabinoid receptor activation reduces the amplitude of voltage-gated calcium currents in the neuroblastoma-glioma cell line NG108-15. The inhibition is potent, being half-maximal at less than 10 nM, and reversible. The inactive enantiomer, WIN 55,212-3, does not reduce calcium currents even at 1 microM. Of the several types of calcium currents in NG108-15 cells, cannabinoids predominantly inhibit an omega-conotoxin-sensitive, high-voltage-activated calcium current. Inhibition was blocked by incubation with pertussis toxin but was not altered by prior treatment with hydrolysis-resistant cAMP analogues together with a phosphodiesterase inhibitor, suggesting that the transduction pathway between the cannabinoid receptor and calcium channel involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. However, the development of inhibition is considerably slower than a pharmacologically similar pathway used by an alpha 2-adrenergic receptor in these cells. Our results suggest that inhibition of N-type calcium channels, which could decrease excitability and neurotransmitter release, may underlie some of the psychoactive effects of cannabinoids.</jats:p> |
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| description | <jats:p>The psychoactive properties of Cannabis sativa and its major biologically active constituent, delta 9-tetrahydrocannabinol, have been known for years. The recent identification and cloning of a specific cannabinoid receptor suggest that cannabinoids mimic endogenous compounds affecting neural signals for mood, memory, movement, and pain. Using whole-cell voltage clamp and the cannabinomimetic aminoalkylindole WIN 55,212-2, we have found that cannabinoid receptor activation reduces the amplitude of voltage-gated calcium currents in the neuroblastoma-glioma cell line NG108-15. The inhibition is potent, being half-maximal at less than 10 nM, and reversible. The inactive enantiomer, WIN 55,212-3, does not reduce calcium currents even at 1 microM. Of the several types of calcium currents in NG108-15 cells, cannabinoids predominantly inhibit an omega-conotoxin-sensitive, high-voltage-activated calcium current. Inhibition was blocked by incubation with pertussis toxin but was not altered by prior treatment with hydrolysis-resistant cAMP analogues together with a phosphodiesterase inhibitor, suggesting that the transduction pathway between the cannabinoid receptor and calcium channel involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. However, the development of inhibition is considerably slower than a pharmacologically similar pathway used by an alpha 2-adrenergic receptor in these cells. Our results suggest that inhibition of N-type calcium channels, which could decrease excitability and neurotransmitter release, may underlie some of the psychoactive effects of cannabinoids.</jats:p> |
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| spelling | Mackie, K Hille, B 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.89.9.3825 <jats:p>The psychoactive properties of Cannabis sativa and its major biologically active constituent, delta 9-tetrahydrocannabinol, have been known for years. The recent identification and cloning of a specific cannabinoid receptor suggest that cannabinoids mimic endogenous compounds affecting neural signals for mood, memory, movement, and pain. Using whole-cell voltage clamp and the cannabinomimetic aminoalkylindole WIN 55,212-2, we have found that cannabinoid receptor activation reduces the amplitude of voltage-gated calcium currents in the neuroblastoma-glioma cell line NG108-15. The inhibition is potent, being half-maximal at less than 10 nM, and reversible. The inactive enantiomer, WIN 55,212-3, does not reduce calcium currents even at 1 microM. Of the several types of calcium currents in NG108-15 cells, cannabinoids predominantly inhibit an omega-conotoxin-sensitive, high-voltage-activated calcium current. Inhibition was blocked by incubation with pertussis toxin but was not altered by prior treatment with hydrolysis-resistant cAMP analogues together with a phosphodiesterase inhibitor, suggesting that the transduction pathway between the cannabinoid receptor and calcium channel involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. However, the development of inhibition is considerably slower than a pharmacologically similar pathway used by an alpha 2-adrenergic receptor in these cells. Our results suggest that inhibition of N-type calcium channels, which could decrease excitability and neurotransmitter release, may underlie some of the psychoactive effects of cannabinoids.</jats:p> Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proceedings of the National Academy of Sciences |
| spellingShingle | Mackie, K, Hille, B, Proceedings of the National Academy of Sciences, Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells., Multidisciplinary |
| title | Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_full | Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_fullStr | Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_full_unstemmed | Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_short | Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| title_sort | cannabinoids inhibit n-type calcium channels in neuroblastoma-glioma cells. |
| title_unstemmed | Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.89.9.3825 |