title: Caffeine analogs: effects on ryanodine-sensitive calcium-release channels and GABAA receptors.
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-Dipropyl-8-cyclopentylxanthine at 100 microM 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.
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Shi
authors.forename: William L
authors.initials: WL
authors.lastname: Padgett
authors.forename: John W
authors.initials: JW
authors.lastname: Daly
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011868:Radioisotopes; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011868:Radioisotopes; D011963:Receptors, GABA-A; D019837:Ryanodine Receptor Calcium Release Channel; D014970:Xanthines; D012433:Ryanodine; D002110:Caffeine; C037476:tert-butylbicyclophosphorothionate; D003975:Diazepam