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Differentiation of pre- and postsynaptic high affinity serotonin receptor binding sites using physico-chemical parameters and modifying agents
- Source :
- Neurochemical Research. 11:891-912
- Publication Year :
- 1986
- Publisher :
- Springer Science and Business Media LLC, 1986.
-
Abstract
- The two 3H-labeled agonists [3H]8-hydroxy-2-(di-n-propylamino) tetralin ([3H]8-OH-DPAT) and [3H]serotonin ([3H]5-HT) have been used to examine the effects of physico-chemical parameters and modulatory agents on the high affinity 5-HT receptor binding sites in various regions of the rat central nervous system. Sites labeled by [3H]8-OH-DPAT and [3H]5-HT were differentially sensitive to changes in incubation temperature and pH, such that the optimal interaction of [3H]8-OH-DPAT with specific sites in the striatum was at 30 degrees C and pH 7.4, whereas [3H]5-HT sites in the same region were most easily labeled at 2-23 degrees C and pH 8.2. Micromolar concentrations of Mn2+ enhanced [3H]5-HT binding but inhibited markedly [3H]8-OH-DPAT binding to striatal membranes. In contrast, both [3H]5-HT and [3H]8-OH-DPAT binding were increased by the cation in hippocampal membranes. Conversely, GTP reduced the binding of either ligand in the hippocampus but affected only [3H]5-HT binding in the striatum. Furthermore, N-ethylmaleimide inhibited equally [3H]5-HT and [3H]8-OH-DPAT binding to hippocampal membranes, but was markedly less potent against [3H]8-OH-DPAT binding to striatal membranes. These results led to the definition of assay conditions for studying separately [3H]8-OH-DPAT binding to "hippocampal-like" (HL) and "striatal-like" (SL) sites. [3H]8-OH-DPAT HL binding sites were particularly abundant in the hippocampus, septum and cerebral cortex, and exhibited pharmacological properties typical of the postsynaptic 5-HT1A subsites previously characterized with [3H]5-HT as the ligand. The regional distribution of [3H]8-OH-DPAT SL binding sites was strikingly different from that of HL sites, but similar to that of serotoninergic terminals identified by their capacity to take up [3H]5-HT. The selective lesion by 5,7-dihydroxytryptamine of serotoninergic projections induced a marked loss of [3H]8-OH-DPAT SL binding sites in the striatum and the cerebral cortex, indicating that these sites were located presynaptically. In contrast, [3H]5-HT binding sites remained unchanged in lesioned rats, which confirmed further their exclusive postsynaptic location in brain.
- Subjects :
- Male
endocrine system
Tetrahydronaphthalenes
GTP'
5,7-Dihydroxytryptamine
Naphthalenes
Hippocampal formation
Biology
Hippocampus
Biochemistry
Serotonin Receptor Binding
Cellular and Molecular Neuroscience
Postsynaptic potential
Animals
Binding site
Cerebral Cortex
8-Hydroxy-2-(di-n-propylamino)tetralin
Manganese
Sulfhydryl Reagents
Temperature
Rats, Inbred Strains
General Medicine
Hydrogen-Ion Concentration
Ligand (biochemistry)
Corpus Striatum
Rats
Receptors, Neurotransmitter
Kinetics
Membrane
nervous system
Receptors, Serotonin
Biophysics
Guanosine Triphosphate
Serotonin
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....6ce84e2e31573a7a93eb064a74a0a771
- Full Text :
- https://doi.org/10.1007/bf00965212