Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg.
2-hydroxycarbazole, a compound structurally related to the Ca2+-mobilizing marine toxin 9-methyl-7-bromoeudistomin, has recently been proposed to activate both type 1 and type 2 ryanodine receptors in skeletal and cardiac muscle, respectively. This study was undertaken to evaluate the activity of th...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1826291305613885440 |
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| author | Thomas, J Churchill, G Patel, S Galione, A |
| author_facet | Thomas, J Churchill, G Patel, S Galione, A |
| author_sort | Thomas, J |
| collection | OXFORD |
| description | 2-hydroxycarbazole, a compound structurally related to the Ca2+-mobilizing marine toxin 9-methyl-7-bromoeudistomin, has recently been proposed to activate both type 1 and type 2 ryanodine receptors in skeletal and cardiac muscle, respectively. This study was undertaken to evaluate the activity of this compound in the sea urchin egg homogenate, a model system used to characterize intracellular Ca2+ mobilization mechanisms. 2-Hydroxycarbazole was found to potently release Ca2+ in a concentration-dependent manner via a specific mechanism displaying apparent desensitization. Use of selective inhibitors of the Ca2+-mobilizing messengers inositol 1,4,5-trisphosphate, cyclic adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate, as well as desensitization of homogenates to each of these molecules, failed to inhibit the response to 2-hydroxycarbazole. However, the response to 2-hydroxycarbazole was competitively antagonized by caffeine. Investigation of the Ca2+ stores accessed by 2-hydroxycarbazole revealed Ca2+ release from a thapsigargin-insensitive pool. Finally, 2-hydroxycarbazole failed to enhance [3H]ryanodine binding, suggesting the operation of a nonryanodine receptor mechanism. These results demonstrate that 2-hydroxycarbazole is acting to modulate a Ca2+ release mechanism with distinct pharmacological properties to those previously reported in the sea urchin egg. |
| first_indexed | 2024-03-07T02:57:27Z |
| format | Journal article |
| id | oxford-uuid:afcf3730-eb31-47f0-a2b1-3052c96e8b0f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:57:27Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:afcf3730-eb31-47f0-a2b1-3052c96e8b0f2022-03-27T03:51:56ZDistinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:afcf3730-eb31-47f0-a2b1-3052c96e8b0fEnglishSymplectic Elements at Oxford2001Thomas, JChurchill, GPatel, SGalione, A2-hydroxycarbazole, a compound structurally related to the Ca2+-mobilizing marine toxin 9-methyl-7-bromoeudistomin, has recently been proposed to activate both type 1 and type 2 ryanodine receptors in skeletal and cardiac muscle, respectively. This study was undertaken to evaluate the activity of this compound in the sea urchin egg homogenate, a model system used to characterize intracellular Ca2+ mobilization mechanisms. 2-Hydroxycarbazole was found to potently release Ca2+ in a concentration-dependent manner via a specific mechanism displaying apparent desensitization. Use of selective inhibitors of the Ca2+-mobilizing messengers inositol 1,4,5-trisphosphate, cyclic adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate, as well as desensitization of homogenates to each of these molecules, failed to inhibit the response to 2-hydroxycarbazole. However, the response to 2-hydroxycarbazole was competitively antagonized by caffeine. Investigation of the Ca2+ stores accessed by 2-hydroxycarbazole revealed Ca2+ release from a thapsigargin-insensitive pool. Finally, 2-hydroxycarbazole failed to enhance [3H]ryanodine binding, suggesting the operation of a nonryanodine receptor mechanism. These results demonstrate that 2-hydroxycarbazole is acting to modulate a Ca2+ release mechanism with distinct pharmacological properties to those previously reported in the sea urchin egg. |
| spellingShingle | Thomas, J Churchill, G Patel, S Galione, A Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg. |
| title | Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg. |
| title_full | Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg. |
| title_fullStr | Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg. |
| title_full_unstemmed | Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg. |
| title_short | Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea urchin egg. |
| title_sort | distinct pharmacology of 2 hydroxycarbazole induced ca2 release in the sea urchin egg |
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