Enhancing effect of zinc on astroglial and cerebral endothelial histamine uptake

Zsuzsanna Huszti, Attila Horváth-Sziklai, Béla Noszál, Emília Madarász, Anna Mária Deli

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have studied the effect of zinc ion on the uptake of histamine (HA) into cultured astroglial and cerebral endothelial cells and established that Zn2+ enhances the uptake of the amine dose-dependently and in remarkable extents by increasing the Vmax to about 3-fold (from 3.25 ± 0.42 to 8.50 ± 0.97 pmol/mg protein/min in astroglial cells) without altering the KM (0.20 ± 0.03 μM) significantly. The stimulatory effect of zinc ion showed strong sensitivity for VUF 8407, an inhibitory compound of astroglial and cerebral endothelial uptake of HA. In the presence of 20 μM VUF 8407 the zinc-enhanced uptake was reduced by about 50% in both cell types. Binding measurements revealed increased capacities of the zinc-exposed HA binding (Bmax= 0.41 ± 0.05 increased to 1.21 ± 0.16 pmol/mg protein in astroglial membranes and Bmax = 0.25 ± 0.03 enhanced to 1.05 ± 0.12 pmol/mg protein in cerebral endothelial membranes) but statistically unchanged affinity of the ligand for HA carrier (KD values calculated as 35.2 ± 3.4 nM and 45.1 ± 3.8 nM for astroglial bindings; whereas 25 ± 2.1 nM and 30 ± 2.6 nM for cerebral endothelial bindings of the amine). The compound VUF 8407 reduced the Bmax of zinc-exposed HA binding of astroglial membranes but did not modify the KD of the zinc-exposed membrane significantly. The ex vivo experiments confirmed our in vitro findings; an i.c.v. dose of 0.4 μmol/kg ZnSO4, 24 hr after the injection, enhanced the uptake of [3H]HA into dissociated hypothalamic and cerebellar cells to about 2- and 3-fold, respectively. Present data clearly showed that zinc exposures enhance the astroglial and the cerebral endothelial uptake of HA in vitro and it might be considered that zinc produces similar effects in vivo. Free zinc may participate in the regulation of the extraneuronal HA concentration and this metal ion (endogenous or exogenous) might be favored in the removal of the amine from the interstitial space especially in conditions with relatively high HA.

Original languageEnglish
Pages (from-to)1491-1500
Number of pages10
JournalBiochemical Pharmacology
Volume62
Issue number11
DOIs
Publication statusPublished - Dec 1 2001

Keywords

  • Cerebral endothelial cells
  • Cultured astroglial cells
  • Histamine uptake
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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