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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 446-454 
    ISSN: 1432-1912
    Keywords: Key words [3H]MDL100 ; 907 ; 5-HT2A receptors ; Rat brain ; Autoradiography ; in situ hybridization ; [3H]ketanserin ; [3H]mesulergine ; [3H]RP62203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 221-224 
    ISSN: 1432-1912
    Keywords: Rat 5-HT1C receptors ; A9 cells ; Desensitization ; Calcineurin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp recording technique. Stimulation of 5-HT1C receptors with serotonin (5-HT) evoked calcium-dependent outward currents of 109 pA in cells clamped at — 50 mV. Pretreatment with the protein kinase C (PKC) activator phorbol myristic acetate (PMA) reduced the 5-HT-induced current amplitude by 46% of the control value. Inclusion of inositol triphosphate (IP3) in the pipette solution induced an outward current of 84 pA. The IP3-induced response was not affected by 60 min pretreatment with PMA. In the presence of the PKC antagonist calphostin C, 60 min treatment with PMA (10−6 mol/1) reduced the 5-HT response only by 8%. In cells preincubated with PMA, injection of the calcium/calmodulin dependent serine proteinphosphatase calcineurin gradually increased the 5-HT-induced responses by 34%. In A9 cells which were incubated 24 h with the 5-HT1C receptor agonist meta chlorophenylpiperazine hydrochloride (mCPP), 5-HT-induced responses were reduced by 23% of the vehicle pretreated control value. Injection of calcineurin in mCPP treated cells enhanced the 5-HT-induced response by 24%. The results suggest that in A9 cells rat 5-HT1C receptors are desensitized after phosphorylation by PKC. This desensitization can be counteracted by calcineurin-induced: dephosphorylation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 486-494 
    ISSN: 1432-1912
    Keywords: Serotonin ; [3H]5-HT ; 5-HT1B and 5-HT1D sites ; Autoradiography ; Species differences ; Basal ganglia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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