Summary
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1)
The binding characteristics of [3H]ketanserin (a reported selective radioligand for serotonin 5-HT2 receptors) and [125I]BE 2254 (which labels selectively α1-adrenoceptors) were characterized in brain frontal cortex membranes of pig and man.
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2)
Saturation experiments indicated that both radioligands label apparently a homogeneous class of binding sites in human and pig fontal cortex membranes.
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3)
Competition experiments with [125I]BE 2254 using 17 agonists and antagonists showed monophasic and steep curves in human and pig frontal cortex membranes. The pharmacological profile of these sites is typical of α1-adrenoceptors.
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4)
In competition experiments with [3H]ketanserin, most of the tested compounds displayed shallow or biphasic curves. In particular, α1-adrenoceptor-selective antagonists (prazosin, WB 4101, BE 2254...) displaced with nanomolar affinity about 15 and 40% of the specific [3H]ketanserin binding in human and pig frontal cortex membranes, respectively.
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5)
The minor component of [3H]ketanserin binding correlated highly significantly with [125I]BE 2254 binding in both membrane preparations.
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6)
The major component of [3H]ketanserin binding to pig and human frontal cortex membranes correlated significantly with [3H]ketanserin binding in rat brain cortex membranes (which is essentially to 5-HT2 receptors).
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7)
The present data demonstrate that [3H]ketanserin in nanomolar concentrations binds significantly to α1-adrenoceptors in human and pig frontal cortex membranes; this suggests a rather limited degree of selectivity of ketanserin for 5-HT2 receptors in pig and human tissues.
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Hoyer, D., Vos, P., Closse, A. et al. [3H]Ketanserin labels 5-HT2 receptors and α1-adrenoceptors in human and pig brain membranes. Naunyn-Schmiedeberg's Arch Pharmacol 335, 226–230 (1987). https://doi.org/10.1007/BF00172788
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DOI: https://doi.org/10.1007/BF00172788