α2-Adrenoceptor subtypes in the human brain: a pharmacological delineation of [3H]RX-821002 binding to membranes and tissue sections

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Abstract

In order to study the characterization and localization of [3H]RX-821002 (2-methoxy-idazoxan) binding to α2-adrenoceptor subtypes in several regions of the human brain, we have carried out competition studies using both autoradiography and membrane binding assays. The α2A-adrenoceptor subtype was found to be predominant in the different layers of the frontal cortex, cerebellum and hippocampal formation, while in the neostriatum it was the non-α2A- (α2B- and α2C-) adrenoceptor subtype. In the frontal cortex, in addition to binding to the α2A-adrenoceptor subtype, [3H]RX-821002 bound also to a small portion of α2B- and α2C-adrenoceptors in layer III, and to an unidentified binding site in the external layers. In the hippocampus, both α2A- and non-α2A- (α2B- and α2C-) adrenoceptors were labelled in the dentate gyrus and the CA1 field, together with 5-HT1A receptors. 5-HT1A receptors were labelled predominantly in the stratum pyramidale layer. These results, in addition to delineate the relative presence of α2-adrenoceptor subtypes, indicate that caution is needed when analyzing RX 821002 binding to human brain tissue.

References (44)

  • J. Pascual et al.

    Quantitative light microscopic autoradiographic localization of α2-adrenoceptors in the human brain

    Brain Res.

    (1992)
  • A. Pazos et al.

    Serotonin receptors in the human brain. III. Autoradiographic mapping of serotonin-1 receptors

    Neuroscience

    (1987)
  • M. Perälä et al.

    Differential expression of two α2-adrenergic receptor subtype mRNAs in human tissues

    Mol. Brain Res.

    (1992)
  • A.C. Petrash et al.

    Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain

    Life Sci.

    (1986)
  • M. Scheinin et al.

    Distribution of α2-adrenergic receptor subtype gene expression in rat brain

    Mol. Brain Res.

    (1994)
  • S. Uhlén et al.

    Delineation of rat kidney α2A- and α2B-adrenoceptors with [3H]RX821002 radioligand binding: computer modelling reveals that guanfacine is an α2A-selective compound

    Eur. J. Pharmacol.

    (1991)
  • G. Vauquelin et al.

    Identification of α2 adrenergic receptors in human frontal cortex membranes by binding of [3H]RX-821002, the 2-methoxy analog of [3H]idazoxan

    Neurochem. Int.

    (1990)
  • M.M. Voigt et al.

    The rat α2-C4 adrenergic receptor gene encodes a novel pharmacologic subtype

    FEBS Lett.

    (1991)
  • P. Young et al.

    Novel α2-adrenoceptor antagonists show selectivity for α2A- and α2B-adrenoceptor subtypes

    Eur. J. Pharmacol.

    (1989)
  • D.E. Berkowitz et al.

    Localization of messenger RNA for three distinct α2-adrenoceptor subtypes in human tissues

    Anesthesiology

    (1994)
  • H.S. Blaxall et al.

    Characterization of the Alpha-2C adrenergic receptor subtype in the oppossum kidney and in the OK cell line

    J. Pharmacol. Exp. Ther.

    (1991)
  • D.B. Bylund et al.

    Alpha-2A and Alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype

    J. Pharmacol. Exp. Ther.

    (1988)
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