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N-methyl-d-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors

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Abstract

In superfused rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline the effect of agonists or antagonists at presynaptic H3 receptors on NMDA-evoked [3H]noradrenaline release was investigated. In experiments on slices, histamine and the preferential H3 receptor agonist R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow (IC20 values 0.27 μmol/l or 0.032 μmol/l, respectively); S-(+)-α-methylhistamine (up to 10 μmol/l) as well as the selective H1 receptor agonist (2-(2-thiazolyl)ethylamine) and the selective H2 receptor agonist dimaprit (each up to 10 μmol/l) were ineffective. The H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H1 receptor antagonist dimetindene and the preferential H2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes, histamine and R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of ω-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(−)-α-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H3 receptors. NMDA receptors and H3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H3 receptor stimulation.

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Reuterstrasse 2b, D-53113, Bonn, Germany

    K. Fink, E. Schlicker & M. Göthert

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  1. K. Fink
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  2. E. Schlicker
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  3. M. Göthert
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Correspondence to: M. Göthert at the above address

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Fink, K., Schlicker, E. & Göthert, M. N-methyl-d-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors. Naunyn-Schmiedeberg's Arch Pharmacol 349, 113–117 (1994). https://doi.org/10.1007/BF00169826

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  • DOI: https://doi.org/10.1007/BF00169826

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