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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 358, Issue 5, pp 574–581 | Cite as

Brain histamine H3 receptors in rats with portacaval anastomosis: in vitro and in vivo studies

  • V. Lozeva
  • Martti Attila
  • Eeva Anttila
  • Kirsti Laitinen
  • Mikko Hippeläinen
  • L. Tuomisto
Original article

Abstract

The long-term effects of portacaval anastomosis (PCA) on histamine H3 receptors in rat brain were studied by in vitro and in vivo methods. The overflow of histamine from the anterior hypothalamus and from cortex after long-term PCA was determined by in vivo microdialysis. The binding properties of [3H]-R-α-methylhistamine in membranes from cortex, cerebellum, and rest of brain (ROB) were examined with saturation binding experiments. The regional distribution of [3H]-R-α-methylhistamine binding sites in the brain of sham- and PCA-operated rats was assessed also with autoradiography. The tissue levels of histamine were significantly elevated in cortex and ROB of PCA-operated rats. In addition, the spontaneous and K+-evoked overflow of histamine from anterior hypothalamus, and the thioperamide-induced overflow from both anterior hypothalamus and cortex were increased after chronic PCA. In spite of the significantly elevated tissue concentrations and the moderate increase in histamine release, the binding properties of [3H]-R-α-methylhistamine to cortical membranes were not significantly changed. However, the autoradiography study did reveal a decrease in [3H]-R-α-methylhistamine binding density, particularly in striatum and cortex, where H3 receptors are located mainly at non-histaminergic neurons. In conclusion, we suggest that there is a region-selective increase in the histaminergic activity in chronic PCA, which leads to the down-regulation of somadendritic and pre-synaptic H3 receptors located at non-histaminergic neurons. At the same time, the autoreceptor mediated control of histamine neuronal activity via pre-synaptic H3 receptors located at histaminergic neurons is preserved after long-term PCA.

Key words Portacaval anastomosis Brain histamine Histamine release Histamine H3 receptors Autoradiography [3H]-R-α-methylhistamine binding Thioperamide Microdialysis 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • V. Lozeva
    • 1
  • Martti Attila
    • 2
  • Eeva Anttila
    • 3
  • Kirsti Laitinen
    • 3
  • Mikko Hippeläinen
    • 4
  • L. Tuomisto
    • 3
  1. 1.Department of Pharmacology, Medical University of Varna, 9002 Varna, BulgariaBG
  2. 2.Department of Clinical Veterinary Sciences, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57 (Hameentie 57), SU-00014 Helsinki, FinlandFI
  3. 3.Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, SU-70211 Kuopio, FinlandFI
  4. 4.Department of Surgery, University Hospital of Kuopio, SU-70211 Kuopio, FinlandFI

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