3H-atipamezole binding sites in mouse cerebral cortex: possible involvement of alpha 2-adrenoceptors in sexual behavior.
Atipamezole is a new specific alpha 2-adrenoceptor antagonist. In this study, first, the presence of specific 3H-atipamezole binding sites in the sagittal and coronal sections of mouse brain was established using autoradiography. In vitro experiments with mouse cerebral cortex membranes indicated that d-medetomidine, a new alpha 2-adrenoceptor agonist structurally related to atipamezole, displaces labelled atipamezole more potently than noradrenaline. The saturation isotherm with d-medetomidine demonstrated high affinity binding with the apparent number of binding sites KD 1.36 nM and 760 fmol/mg, respectively. In the next series of experiments male mice were sacrificed immediately after copulation and cerebral cortex 3H-atipamezole and 3H-flumazenil binding was studied. Oxymetazoline and prazosin are known to label preferably alpha 2A and alpha 2B subtypes of alpha 2-adrenoceptors. Therefore, parallelly with noradrenaline both these compounds were used to determine non-specific binding of 3H-atipamezole. When noradrenaline or oxymetazoline were used as displacing agents copulation caused a significant increase of 3H-atipamezole binding sites. No significant changes were observed when prazosin was used. 3H-Flumazenil binding remained unchanged by copulation. The up-regulation of 3H-atipamezole binding sites indicates that not only alpha 2-adrenoceptors in the periphery but also in the CNS may participate in the regulation of sexual behavior. Moreover, in regulation of sexual behavior central alpha 2-adrenoceptors may be more important than benzodiazepine receptors.
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
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Rägo
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Saano
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Tupala
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Nieminen
M M
MM
Airaksinen
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000737:chemistry*; D005260:Female; D007093:Imidazoles / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000502:physiology*; D014316:Tritium; D015854:Up-Regulation
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C050701:atipamezole; D014316:Tritium