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  • Autoradiography  (2)
  • 5-HT1D sites  (1)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 446-454 
    ISSN: 1432-1912
    Schlagwort(e): Key words [3H]MDL100 ; 907 ; 5-HT2A receptors ; Rat brain ; Autoradiography ; in situ hybridization ; [3H]ketanserin ; [3H]mesulergine ; [3H]RP62203
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The recently developed 5-HT2A receptor selective antagonist [3H]MDL100,907 ((+/–)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol]) has been characterized as a radioligand for the autoradiographic visualization of these receptors. [3H]MDL100,907 binding to rat brain tissue sections was saturable, had sub-nanomolar affinity (Kd=0.2–0.3nM), and presented a pharmacological profile consistent with its binding to 5-HT2A receptors (rank order of affinity for [3H]MDL100,907-labelled receptors: MDL100,907 〉 spiperone 〉 ketanserin 〉 mesulergine). The distribution of receptors labelled by [3H]MDL100,907 was compared to the autoradiographical patterns obtained with [3H]Ketanserin, [3H]Mesulergine, and [3H]RP62203 (N-[3-[4-(4-fluorophenyl)-piperazin-1-y1]propyl]-1,8-naphtalenesultam) and to the distribution of 5-HT2A receptor mRNA as determined by in situ hybridization. As opposed to the other radioligands, [3H]MDL100,907 labelled a single population of sites (5-HT2A receptors) and presented extremely low levels of non-specific binding. The close similarity of the distributions of [3H]MDL100,907-labelled receptors and 5-HT2A mRNA further supports the selectivity of this radioligand for 5-HT2A receptors and suggests a predominant somatodendritic localization of these receptors. The present results point to [3H]MDL100,907 as the ligand of choice for the autoradiographic visualization of 5-HT2A receptors.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 595-601 
    ISSN: 1432-1912
    Schlagwort(e): [3H]5-HT binding ; Human ; Pig and calf brain ; 5-HT1A ; 5-HT1B ; 5-HT1C ; 5-HT1D sites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1) The binding characteristics of [3H]5-HT (5-hydroxytryptamine, serotonin) were investigated in membrane preparations of several regions from calf, pig and human brain in the presence of 100 nmol/l 8-OH-DPAT (8-hydroxy-2[di-n-dipropylamino]tetralin) and 100 nmol/l mesulergine in order to mask 5-HT1A and 5-HT1C sites. 2) [3H]5-HT bound rapidly, reversibly and stereo-selectively to a population of high affinity recognition sites in membranes from pig caudate, calf caudate and human cortex, caudate and substantia nigra. 3) Saturation experiments carried out with [3H]5-HT in the presence of 100 nmol/l 8-OH-DPAT and 100 nmol/l mesulergine revealed that non-5-HT1A non-5-HT1C sites represented from 50 to more than 90% of the total 5-HT1 sites (determined with [3H]5-HT in the absence of 8-OHDPAT and mesulergine), depending on the tissue source. 4) The pharmacological profile of these sites was characterized in competition experiments performed with a variety of ligands in membranes of calf, pig and human caudate membranes. Under these conditions, [3H]5-HT labelled a population of “5-HT1-like” sites which display nanomolar affinity for tryptamines (5-carboxamidotryptamine 〉 5-HT 〉- 5-methoxytryptamine 〉 tryptamine) and some ergolines (metergoline 〉 methysergide). In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT1A (8-OH-DPAT, buspirone), 5-HT1B (21-009, RU 24969), 5-HT1C (mesulergine, mianserin) and 5-HT2 sites (ketanserin, cinanserin). 5) Non-5-HT1A non-5-HT1C sites from calf, pig and human caudate membranes displayed a closely similar affinity profile as illustrated by the statistically very significant correlation parameters obtained when they were compared to one another. The pharmacological profile of these sites is different from that of 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2 and 5-HT3 sites but is consistent with the pharmacology of a “5-HT1-like” receptor. It is very similar to that of the 5-HT1D site recently described in bovine brain by Heuring and Peroutka (1987). 6) The present findings demonstrate the presence and the pharmacological similarity of 5-HT1D sites in pig, calf and human brain.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 486-494 
    ISSN: 1432-1912
    Schlagwort(e): Serotonin ; [3H]5-HT ; 5-HT1B and 5-HT1D sites ; Autoradiography ; Species differences ; Basal ganglia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The regional distribution of high affinity [33H]5-HT recognition sites in the brain of several vertebrates (pigeon, rat, mouse, guinea-pig, cat, dog, monkey and human) was analyzed using in vitro autoradiography. The presence of subtypes of 5-HT1 binding sites was investigated by selective displacements with 8-OH-DPAT, mesulergine and (±)SDZ 21-009 at appropriate concentrations to block 5-HT1A, 5-HT1c and 5-HT1B sites respectively. In addition, 5-HT1A, and 5-HT1c sites were directly visualized with the more selective radioligands [3H]8-OH-DPAT and [3H]mesulergine, respectively. In the pigeon brain, total [3H]5-HT binding sites were enriched in all telencephalic areas. Densely labelled regions were also present in the optic tectum and the brainstem. No binding was observed in the cerebellum. 8-OH-DPAT and mesulergine only displaced a small proportion of [3H]5-HT binding in most of the areas where high concentrations of 5-HT1 sites were found. (±)SDZ 21-009 did not affect [3H]5-HT binding in the regions examined. Taking into account our pharmacological studies, these results suggest that the majority of 5-HT1 sites belong to the 5-HT1D subtype in the pigeon brain. In the mammalian species investigated high levels of [3H]5-HT binding were found in the neo-cortex, hippocampal formation, basal ganglia and related structures (substantia nigra), raphe dorsalis, nucleus superior colliculus and choroid plexus. However, these brain areas were differentially enriched in subtypes of 5-HT1 recognition sites. 5-HT1A sites were observed in the neo-cortex, the hippocampal formation and the raphe nucleus, whereas 5-HT1C sites accounted for all 5-HT1 binding in the choroid plexus. In the mouse and rat brain, 5-HT1B binding sites were enriched in the basal ganglia and associated regions (substantia nigra). These areas were enriched in 5-HT1D sites in the brain of the other mammals studied. In these animals, no site with a 5-HT1B pharmacological profile were detected. These results indicate that 5-HT1A 5-HT1c and 5-HT1D sites are present already in the lower vertebrate species investigated and that 5-HT1B appear to be exclusive of the myomorph rodents (mouse, rat). Furthermore, the different subtypes of the 5-HT1, receptors present a conserved regional distribution with the 5-HT1D sites being enriched in the basal ganglia and the 5-HT1A sites predominating in the hippocampal formation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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