Adaptive changes in the number of Gs- and Gi-proteins underlie adenylyl cyclase sensitization in morphine-treated rat striatal neurons
| Autor: | Angélique L.C.T. Van Rijswijk, Arie H. Mulder, George Wardeh, Anton N. M. Schoffelmeer, Vliet Bernard J Van |
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| Rok vydání: | 1993 |
| Předmět: |
Agonist
medicine.medical_specialty G protein medicine.drug_class medicine.disease_cause Adenylyl cyclase Mice Radioligand Assay chemistry.chemical_compound GTP-Binding Proteins Dopamine Internal medicine Cyclic AMP medicine Animals Rats Wistar Cells Cultured Pharmacology Analysis of Variance Forskolin Morphine Receptors Dopamine D1 Cholera toxin ADCY9 Drug Tolerance Corpus Striatum Rats medicine.anatomical_structure Endocrinology chemistry 2 3 4 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine Neuron Morphine Dependence Adenylyl Cyclases medicine.drug |
| Zdroj: | European Journal of Pharmacology: Molecular Pharmacology. 245:23-29 |
| ISSN: | 0922-4106 |
| Popis: | In the present study we investigated the possible role of changes in the number of membrane-bound G-proteins in the sensitization of dopamine D 1 receptor-stimulated adenylyl cyclase, observed in primary cultures of rat striatal neurons chronically exposed to morphine. Whereas exposure of these neurons to 10 μM morphine for 7 days caused a profound increase in cyclic AMP production, induced by the dopamine D 1 receptor agonist SKF 38393 (1 μM), Scatchard analysis of [ 125 I]SCH 23982 binding to membrane preparations revealed that neither the B max nor the K d values of dopamine D 1 receptor binding sites were affected. Interestingly, immunoblotting experiments revealed an increase (of more than 50%) in the number of stimulatory G-proteins (G αs ) in neurons displaying an enhanced adenylyl cyclase activity. In morphine-treated neurons, the number of inhibitory G-proteins (G αi ) appeared to be slightly reduced (by about 16%). Moreover, the observation that cholera toxin (0.1 nM)-stimulated cyclic AMP production, unlike that induced by forskolin (1 μM), was enhanced in morphine-treated neurons, indicates a causal relationship between the reciprocal changes in G-protein number and the increase of dopamine D 1 receptor-stimulated adenylyl cyclase activity. The possible role of these changes in G-protein number in the development of morphine tolerance and dependence is discussed. |
| Databáze: | OpenAIRE |
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