8-bromo-cAMP and 8-CPT-cAMP increase the density of beta-adrenoceptors in hepatocytes by a mechanism not mimicking the effect of cAMP
| Autor: | Magne Refsnes, Dagny Sandnes, Thoralf Christoffersen, Frede W. Jacobsen |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Cell Survival Phosphodiesterase Inhibitors Health Toxicology and Mutagenesis 8-Bromo Cyclic Adenosine Monophosphate Adenosine kinase Toxicology Glucagon Binding Competitive β adrenoceptor chemistry.chemical_compound Deoxyadenosine Internal medicine 1-Methyl-3-isobutylxanthine Receptors Adrenergic beta medicine Cyclic AMP Animals Phosphodiesterase inhibitor Rats Wistar Cells Cultured Pharmacology Forskolin biology 8-CPT-cAMP Thionucleotides Rats Endocrinology chemistry Liver biology.protein Intracellular Adenylyl Cyclases |
| Zdroj: | Pharmacologytoxicology. 79(1) |
| ISSN: | 0901-9928 |
| Popis: | Addition of 8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) or 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8-CPT-cAMP) to hepatocytes at the time of plating enhanced the acquisition of beta-adrenoceptors that occurs spontaneously upon culturing as primary monolayers. This effect was partially suppressed by the phosphodiesterase inhibitor isobutyl methylxanthine, and was mimicked by 8-bromo-AMP, 8-bromo-adenosine, and the adenosine kinase inhibitor 5'-amino-5'-deoxyadenosine. Agents that elevated the intracellular level of cAMP, such as glucagon and forskolin, and Sp-8-bromo-adenosine 3',5'-monophosphorothioate (Sp-8-bromo-cAMPS), a cAMP analogue that is resistant towards metabolic breakdown, did not significantly enhance beta-adrenoceptor expression when used alone, but glucagon enhanced the effect of 8-bromo-adenosine. 8-bromo-cAMP and 8-bromo-adenosine decreased cellular ATP-levels. These observations suggest that the enhanced beta-adrenoceptor acquisition was mediated mainly through the action of metabolites of 8-bromo-cAMP and 8-CPT-cAMP, although there may be a cAMP-mediated component in the effect. Several mechanisms, including depletion of ATP, are probably involved, and might affect beta-adrenoceptor degradation. |
| Databáze: | OpenAIRE |
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