Caffeine analogs: effects on ryanodine-sensitive calcium-release channels and GABAA receptors |
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Authors: | Shi Dan Padgett William L Daly John W |
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Institution: | (1) Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA |
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Abstract: | 1. Caffeine at 0.3–10 mM enhanced the binding of 3H]ryanodine to calcium-release channels of rabbit muscle sarcoplasmic reticulum. A variety of other xanthines were as efficacious as caffeine or nearly so, but none appeared markedly more potent.2. Caffeine at 1 mM markedly inhibited binding of 3H]diazepam to GABAA receptors in rat cerebral cortical membranes.3. Other xanthines also inhibited binding with certain dimethylpropargylxanthines being nearly fivefold more potent than caffeine.4. Caffeine at 1 mM stimulated binding of 35S]TBPS to GABAA receptors as did certain other xanthines.5. The dimethylpropargylxanthines had little effect. 1,3-Dipropy1-8-cyclopentylxan- thine at 100 M had no effect on 3H]diazepam binding, but markedly inhibited 35S]TBPS binding.6. Structure–activity relationships for xanthines do differ for calcium-release channels and and for different sites on GABAA receptors, but no highly selective lead compounds were identified. |
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Keywords: | caffeine xanthines diazepam ryanodine GABA receptors calcium-release channels |
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