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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ishibashi, M. Takahashi, Y. Furukawa, K. Kobayashi, J. Kozutsumi, D. Ohizumi, Y. |
| Description | Author Affiliation: Takahashi Y ( Department of Pharmaceutical Molecular Biology, Tohoku University, Sendai, Japan.) |
| Abstract | 1. 4,6-Dibromo-3-hydroxycarbazole (DBHC) was synthesized as an analogue of bromoeudistomin D (BED), a powerful Ca2+ releaser, and its pharmacological properties were examined. 2. In Ca2+ electrode experiments, DBHC (100 microM) markedly inhibited Ca2+ release from the heavy fraction of sarcoplasmic reticulum (HSR) induced by caffeine (1 mM) and BED (10 microM). 3. DBHC (0.1 to 100 microM) inhibited 45Ca2+ release induced by Ca2+ from HSR in a concentration-dependent manner. 4. DBHC (100 microM) abolished 45Ca2+ release induced by caffeine (1 mM) and BED (10 microM) in HSR. 5. Inhibitory effects of calcium-induced calcium release (CICR) blockers such as procaine, ruthenium red and Mg2+ on 45Ca2+ release were clearly observed at Ca2+ concentrations from pCa 7 to pCa 5.5, and were decreased at Ca2+ concentrations higher than pCa 5.5 or lower than pCa 7. However, DBHC decreased Ca2+ release induced by Ca2+ over the wide range of extravesicular Ca2+ concentrations. 6. [3H]-ryanodine binding to HSR was suppressed by ruthenium red, Mg2+ and procaine, but was not affected by DBHC up to 100 microM. 7. [3H]-ryanodine binding to HSR was enhanced by caffeine and BED. DBHC antagonized the enhancement in a concentration-dependent manner. 8. 9-[3H]-Methyl-7-bromo-eudistomin D, an 3H-labelled analogue of BED, specifically bound to HSR. Both DBHC and caffeine increased the KD value without affecting the Bmax value, indicating a competitive mode of inhibition. 9. These results suggest that DBHC binds to the caffeine binding site to block Ca2+ release from HSR. This drug is a novel type of inhibitor for the CICR channels in SR and may provide a useful tool for clarifying the Ca2+ releasing mechanisms in SR. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 114 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1995-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Caffeine Pharmacology Calcium Antagonists & Inhibitors Metabolism Carbazoles Muscle, Skeletal Sarcoplasmic Reticulum Animals Calcium Radioisotopes Carbolines In Vitro Techniques Ion-Selective Electrodes Magnesium Drug Effects Procaine Rabbits Ruthenium Red Ryanodine Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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