Characterization of Histamine Release from the Rat Hypothalamus as Measured by In Vivo Microdialysis

Yoshinori Itoh, Ryozo Oishi, Masahiro Nishibori, Kiyomi Saeki

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104 Citations (Scopus)

Abstract

Abstract: The release of endogenous histamine (HA) from the hypothalamus of anesthetized rats was measured by in vivo microdialysis coupled with HPLC with fluorescence detection. Freshly prepared Ringer's solution was perfused at a rate of 1 μl/min immediately after insertion of a dialysis probe into the medial hypothalamus, and brain perfusates were collected every 30 min into microtubes containing 0.2 M perchloric acid. The basal HA output was almost constant between 30 min and 7 h after the start of perfusion, with the mean value being 7.1 pg/30 min. Thus, the extracellular HA concentration was assumed to be 7.8 nM, by a calculation from in vitro recovery through the dialysis membrane. Perfusion with a high K+ (100 mM)‐containing medium increased the HA output by 170% in the presence of Ca2+. Systemic administration of either thioperamide (5 mg/kg, i.p.), a selective H3 receptor antagonist, or metoprine (10 mg/kg, i.p.), an inhibitor of HA‐N‐methyltransferase, caused an approximately twofold increase in the HA output 30–60 min after treatment. The combined treatment with thioperamide and metoprine produced a marked increase (650%) in the HA output. The HA output decreased by ∼70% 4–5 h after treatment with α‐fluoromethylhistidine (α‐FMH; 100 mg/kg, i.p.), an inhibitor of histidine decarboxylase. Furthermore, the effect of combined treatment with thioperamide and metoprine was no longer observed in α‐FMH‐treated rats. These results suggest that both HA‐N‐methyltransferase and H3 autoreceptors are involved in maintaining a constant level of extracellular HA and that their blockade effectively results in a higher activity level of the endogenous histaminergic system in the CNS.

Original languageEnglish
Pages (from-to)769-774
Number of pages6
JournalJournal of Neurochemistry
Volume56
Issue number3
DOIs
Publication statusPublished - Mar 1991

Keywords

  • H receptors
  • Histamine
  • Histamine‐N‐methyl‐transferase
  • Hypothalamus
  • Microdialysis
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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