Summary
The high-affinity binding of3H-serotonin and3H-DP-AT was studied in membrane preparations and tissue sections of cerebral cortex and basal ganglia of human brain. In tissue sections,3H-serotonin bound to sites present at high density in the cerebral cortex, hippocampus and basal ganglia.3HDPAT bound predominantly to the outer layers of the cerebral cortex and the hippocampus, no significant binding was observed in the basal ganglia. In cortical membranes3H-serotonin bound to a heterogeneous population of sites, one of which was similar to a binding site labelled by3H-DPAT (the putative 5HT-1A receptor).3H-serotonin binding to membranes prepared from the putamen displayed low affinity for DPAT, mesulergine and spiperone, RU 24969 was considerably less potent than serotonin itself. This3H-serotonin binding site does not have the properties of those sites described in rodent brain (5 HT-1 A, 5 HT-1 B, and 5 HT-1 C), and may represent a novel serotoninergic binding site.
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References
Bennett JP, Snyder SJ (1976) Serotonin and lysergic acid diethylamide binding in rat brain membranes: relationship to postsynaptic serotonin receptors. Mol Pharmacol 12: 373–389
Biegon A, Kargman S, Snyder L, McEwen BS (1986) Characterization and localization of serotonin receptors in human brain post-mortem. Brain Res 363: 91–98
Charlton KG, Bond RA, Clarke DE (1986) An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney. Naunyn Schmiedebergs Arch Pharmacol 332: 8–15
Clineschmidt BV, Reiss DR, Pettibone DJ, Robinson, JL (1985) Characterization of 5- hydroxytryptamine receptors in rat stomach fundus. J Pharmacol Exp Ther 235: 696–708
Cross AJ (1983) Interactions of3H-LSD with serotonin receptors in human brain. Eur J Pharmacol 82: 77–80
Cross AJ, Reynolds GP, Hewitt LM, Slater P (1986) Brain serotonin receptor in Huntington's disease. Neurochem Int 9: 431–435
Cross AJ (1987) Serotonin in neurodegenerative disorders. In: Osborne NN, Hamon M (eds) Neuronal serotonin. Wiley, New York pp 231–253
De Vivo M, Maayani S (1986) Characterization of the 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes. J Pharmacol Exp Ther 238: 248–253
Engel G, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn Schmiedebergs Arch Pharmacol 332: 1–7
Fillon GMB, Rouselle J, Fillion M, Beaudoin DM, Goiny MR, Deniau J, Jacob JJ (1978) High-affinity binding of3H-5-hydroxytryptamine to brain synaptosomal membranes: comparison with3H-lysergic acid diethylamide binding. Mol Pharmacol 14: 50–59
Gothert M, Schlicker E (1983) Autoreceptor-mediated inhibition of3H-5-hydroxytryptamine release from rat brain cortex slices by analogues of 5-hydroxytryptamine. Life Sci 32: 1183–1191
Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M (1983) Identification of presynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature 305: 140–142
Heuring RE, Peroutka SJ (1987) Characterization of a novel3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci 1: 894–903
Heuring RE, Schlegel JR, Peroutka SJ (1986) Species variations in RU 24969 interactions with non-5-HT1A binding sites. Eur J Pharmacol 122: 279–282
Hoyer D, Engel G, Kalkman HO (1985) Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig bran membranes: radioligand binding studies with [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol 118: 13–23
Hoyer D, Pazos A, Probst A, Palacios JM (1986a) Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res 376: 85–96
Hoyer D, Pazos A, Probst A, Palacios JM (1986b) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376: 97–107
Kohler C, Radesater A-C, Lang W, Chan-Palay V (1986) Distribution of serotonin-1 A receptors in the monkey and the post mortem human hippocampal region. A quantitative autoradiographic study using the selective agonist [3H]8-OH-DPAT. Neurosci Lett 72: 43–48
Middlemiss DN, Fozard J (1983) 8-Hydroxy-2-(di-n-propyl-amino)tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol 90: 151–153
Middlemiss DN (1986) Functional correlates of the subtypes of the 5-HT1 recognition site. Trends Pharm Sci 7: 52–53
Palacios JM, Niehoff DL, Kuhar MJ (1981) [3H]Spiperone binding sites in brain: utoradiographic localization of multiple receptors. Brain Res 213: 277–289
Palacios JM, Pazos A, Hoyer D (1987) Characterization and mapping of 5HT-1 A sites in the brain of animals and man. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain serotonergic mechanisms: the pharmacological, biochemical and potential therapeutic actions of 8-OH-DPAT. Ellis Horwood, Chichester, England, pp 67–81
Pazos A, Hoyer D, Palacios J (1984) The binding of serotonergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur J Pharmacol 106: 539–546
Pazos A, Probst A, Palacios JM (1987) Serotonin receptors in the human brain. III Autoradiographic mapping of serotonin-1 receptors. Neuroscience 21: 97–122
Pedigo NW, Yamamura HI, Nelson DL (1981) Discrimination of multiple3H-5-hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain. J Neurochem 36: 220–226
Peroutka SJ, Snyder SH (1979a) Multiple serotonin receptors: differential binding of3H-serotonin,3H-lysergic acid diethylamide and3H-spiroperidol. Mol Pharmacol 16: 687–699
Peroutka SJ (1986) Pharmacological differentiation and characterization of 5 HT-1 A, 5 HT-1 B and 5HT-1 C binding sites in rat frontal cortex. J Neurochem 47: 529–540
Reisine TD, Fields JZ, Yamamura HI, Bird ED, Spokes E, Schreiner PS, Enna SJ (1977) Neurotransmitter receptor alterations in Parkinson's disease. Life Sci 21: 335–344
Schlicker E, Brandt F, Classen K, Gothert M (1985) Serotonin release in human cerebral cortex and its modulation via serotonin receptors. Brain Res 331: 337–341
Slater P (1985) A microcomputer-based image analyser for receptor autoradiography. Br J Pharmacol 85: 391 P
Whitaker PM, Seeman P (1978) High-affinity3H-serotonin binding to caudate: inhibition by hallucinogens and serotonergic drugs. Psychopharmacology 59: 1–5
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Cross, A.J., Slater, P. High affinity serotonin binding sites in human brain: a comparison of cerebral cortex and basal ganglia. J. Neural Transmission 76, 211–219 (1989). https://doi.org/10.1007/BF01260506
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DOI: https://doi.org/10.1007/BF01260506