Identification of α1L-adrenoceptor in mice and its abolition by α1A-adrenoceptor gene knockout

Authors

  • I Muramatsu,

    Corresponding author
    1. Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui School of Medicine, Eiheiji, Fukui, Japan
      Division of Pharmacology, Department of Biochemistry and Bioinformative Science, University of Fukui School of Medicine, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan. E-mail: muramatu@u-fukui.ac.jp
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  • S Morishima,

    1. Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui School of Medicine, Eiheiji, Fukui, Japan
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  • F Suzuki,

    1. Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui School of Medicine, Eiheiji, Fukui, Japan
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  • H Yoshiki,

    1. Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui School of Medicine, Eiheiji, Fukui, Japan
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  • A S M Anisuzzaman,

    1. Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui School of Medicine, Eiheiji, Fukui, Japan
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  • T Tanaka,

    1. Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui School of Medicine, Eiheiji, Fukui, Japan
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  • M C Rodrigo,

    1. Cardiology Division and Research Service, Veterans Affairs Medical Center, San Francisco, CA, USA
    2. Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA, USA
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  • B E Myagmar,

    1. Cardiology Division and Research Service, Veterans Affairs Medical Center, San Francisco, CA, USA
    2. Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA, USA
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  • P C Simpson

    1. Cardiology Division and Research Service, Veterans Affairs Medical Center, San Francisco, CA, USA
    2. Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA, USA
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Division of Pharmacology, Department of Biochemistry and Bioinformative Science, University of Fukui School of Medicine, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan. E-mail: muramatu@u-fukui.ac.jp

Abstract

Background and purpose:

The α1L-adrenoceptor has pharmacological properties that distinguish it from three classical α1-adrenoceptors (α1A, α1B and α1D). The purpose of this was to identify α1L-adrenoceptors in mice and to examine their relationship to classical α1-adrenoceptors.

Experimental approach:

Radioligand binding and functional bioassay experiments were performed on the cerebral cortex, vas deferens and prostate of wild-type (WT) and α1A-, α1B- and α1D-adrenoceptor gene knockout (AKO, BKO and DKO) mice.

Key results:

The radioligand [3H]-silodosin bound to intact segments of the cerebral cortex, vas deferens and prostate of WT, BKO and DKO but not of AKO mice. The binding sites were composed of two components with high and low affinities for prazosin or RS-17053, indicating the pharmacological profiles of α1A-adrenoceptors and α1L-adrenoceptors. In membrane preparations of WT mouse cortex, however, [3H]-silodosin bound to a single population of prazosin high-affinity sites, suggesting the presence of α1A-adrenoceptors alone. In contrast, [3H]-prazosin bound to two components having α1A-adrenoceptor and α1B-adrenoceptor profiles in intact segments of WT and DKO mouse cortices, but AKO mice lacked α1A-adrenoceptor profiles and BKO mice lacked α1B-adrenoceptor profiles. Noradrenaline produced contractions through α1L-adrenoceptors with low affinity for prazosin in the vas deferens and prostate of WT, BKO and DKO mice. However, the contractions were abolished or markedly attenuated in AKO mice.

Conclusions and implications:

α1L-Adrenoceptors were identified as binding and functional entities in WT, BKO and DKO mice but not in AKO mice, suggesting that the α1L-adrenoceptor is one phenotype derived from the α1A-adrenoceptor gene.

British Journal of Pharmacology (2008) 155, 1224–1234; doi:10.1038/bjp.2008.360; published online 22 September 2008

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