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A search for functional histamine H4 receptors in the human, guinea pig and mouse brain

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Abstract

Histamine H4 receptors are expressed in immune cells, but their potential role in the brain is less clear. Although H4 transcripts have been identified in human and rat brain, the presence of H4 receptors on the protein level has so far not been proven since appropriate antibodies fulfilling the strict criteria for G protein-coupled receptors are missing. Here, we searched for functional H4 receptors in human, guinea pig and mouse cortex. We studied whether H4 receptor activation is associated with increased GTPγS binding and reduced noradrenaline release. The latter two effects have been previously shown for H3 receptors, which, like the H4 receptors, are coupled to G i/o protein. G protein activation was studied using 35S-GTPγS binding in cortical membranes. The electrically induced 3H-noradrenaline release was determined in superfused cortical slices. The H4 agonist 4-methylhistamine failed to affect 35S-GTPγS binding and/or noradrenaline release in human, guinea pig and mouse cortex although an H 3 receptor-mediated increase in 35S-GTPγS binding and inhibition of noradrenaline release occurred in parallel experiments. In conclusion, functional H4 receptors increasing 35S-GTPγS binding and/or decreasing noradrenaline release are not found in human, guinea pig and mouse cortex.

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Acknowledgements

The financial support of V.S. and E.S. by the faculty programme BONFOR is gratefully acknowledged. We would also like to thank Mrs. D. Petri for her skilled assistance and Schering-Plough Research for a gift of thioperamide.

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Author notes

  1. Marec von Lehe

    Present address: Neurochirurgische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892, Bochum, Germany

Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Monika Feliszek, Valerie Speckmann, Daniel Schacht & Eberhard Schlicker

  2. Neurochirurgische Klinik, Universität Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Marec von Lehe

  3. Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany

    Holger Stark

Authors
  1. Monika Feliszek
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  2. Valerie Speckmann
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  3. Daniel Schacht
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  4. Marec von Lehe
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  5. Holger Stark
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  6. Eberhard Schlicker
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Correspondence to Eberhard Schlicker.

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Feliszek, M., Speckmann, V., Schacht, D. et al. A search for functional histamine H4 receptors in the human, guinea pig and mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 388, 11–17 (2015). https://doi.org/10.1007/s00210-014-1053-6

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  • DOI: https://doi.org/10.1007/s00210-014-1053-6

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