Autoradiography of Serotonin 5-HT1A Receptor-Activated G Proteins in Guinea Pig Brain Sections by Agonist-Stimulated [35S]GTPγS Binding
Autor: | Christiane Palmier, Delphine S. Dupuis, Petrus J. Pauwels, Francis Colpaert |
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Rok vydání: | 2002 |
Předmět: |
Male
Agonist medicine.medical_specialty G protein medicine.drug_class Guinea Pigs GTPgammaS Biology Sulfur Radioisotopes Hippocampus Biochemistry Piperazines Cellular and Molecular Neuroscience chemistry.chemical_compound Dorsal raphe nucleus GTP-Binding Proteins Flesinoxan Internal medicine medicine Animals Inverse agonist Brain Chemistry 8-Hydroxy-2-(di-n-propylamino)tetralin Oxadiazoles Tryptamines Serotonin Receptor Agonists Endocrinology nervous system chemistry Guanosine 5'-O-(3-Thiotriphosphate) Receptors Serotonin Receptor Serotonin 5-HT1B Autoradiography Raphe Nuclei 5-HT1A receptor Septal Nuclei Serotonin Receptors Serotonin 5-HT1 medicine.drug |
Zdroj: | Journal of Neurochemistry. 70:1258-1268 |
ISSN: | 1471-4159 0022-3042 |
Popis: | G protein activation mediated by serotonin 5-HT1A and 5-HT(1B/D) receptors in guinea pig brain was investigated by using quantitative autoradiography of agonist-stimulated [35S]GTPgammaS binding to brain sections. [35S]GTPgammaS binding was stimulated by the mixed 5-HT1A/5-HT(1B/D) agonist L694247 in brain structures enriched in 5-HT1A binding sites, i.e., hippocampus (+140 +/- 14%), dorsal raphe (+70 +/- 8%), lateral septum (+52 +/- 12%), cingulate (+36 +/- 8%), and entorhinal cortex (+34 +/- 5%). L694247 caused little or no stimulation of [35S]GTPgammaS binding in brain regions with high densities of 5-HT(1B/D) binding sites (e.g., substantia nigra, striatum, central gray, and dorsal subiculum). The [35S]GTPgammaS binding response was antagonized by WAY100635 (10 microM) and methiothepin (10 microM). In contrast, the 5-HT1B inverse agonist SB224289 (10 microM) did not affect the L694247-mediated [35S]GTPgammaS binding response, and the mixed 5-HT(1B/D) antagonist GR127935 (10 microM) yielded a partial blockade. The distribution pattern of the [35S]GTPgammaS binding response and the antagonist profile suggest the L694247-mediated response in guinea pig brain to be mediated by 5-HT1A receptors. In addition to L694247, 8-hydroxy-2-(di-n-propylamino)tetralin, and flesinoxan also stimulated [35S]GTPgammaS binding; their maximal responses varied between 46 and 52% compared with L694247, irrespective of the brain structure being considered. Sumatriptan, rizatriptan, and zolmitriptan (10 microM) stimulated [35S]GTPgammaS binding in the hippocampus by 20-50%. Naratriptan, CP122638, and dihydroergotamine stimulated [35S]GTPgammaS binding to a similar level as L694247 in hippocampus, lateral septum, and dorsal raphe. It appears that under the present experimental conditions, G protein activation through 5-HT1A but not 5-HT(1B/D) receptors can be measured in guinea pig brain sections. |
Databáze: | OpenAIRE |
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