Carrier-mediated release of monoamines induced by the nicotinic acetylcholine receptor agonist DMPP

Bernadett K. Szász, Aliz Mayer, G. Zsilla, Balázs Lendvai, E. Vízi, János P. Kiss

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We have previously shown that dimethylphenylpiperazinium (DMPP) increases the release of noradrenaline (NA) from rat hippocampal slices via two distinct mechanisms: a nicotinic acetylcholine receptor (nAChR)-mediated exocytosis and a carrier-mediated release induced by the reversal of NA transporters. Our aim was to investigate whether other monoaminergic systems are also affected by the multiple actions of DMPP. In our experiments DMPP dose-dependently increased the release of dopamine (DA) and serotonin (5-HT) from rat striatal and hippocampal slices, respectively. The dual effect was observed, however, only in case of DA at a lower DMPP concentration (30 μM), where the response was partly inhibited by mecamylamine, TTX and Ca2+-free medium (nAChR-mediated exocytosis) while the other part of the response was blocked only by the DA uptake inhibitor nomifensine (carrier-mediated release). In contrast, the DMPP-evoked 5-HT release and the DA release induced by high concentration DMPP was not inhibited by nicotinic antagonists, TTX and Ca2+-free medium but only by selective uptake inhibitors. In addition, DMPP dose-dependently inhibited the [3H]DA and [3H]5-HT uptake in striatal and hippocampal synaptosome preparation with an IC50 of 3.18 and 0.49 μM, respectively. Our data show that DMPP interacts with monoamine transporters and induces a substantial carrier-mediated release of DA and 5-HT, therefore caution is needed for the interpretation of data, when this drug is used as a nAChR agonist.

Original languageEnglish
Pages (from-to)400-409
Number of pages10
JournalNeuropharmacology
Volume49
Issue number3
DOIs
Publication statusPublished - Sep 2005

Fingerprint

Dimethylphenylpiperazinium Iodide
Cholinergic Agonists
Nicotinic Receptors
Dopamine
Serotonin
Corpus Striatum
Exocytosis
Dopamine Uptake Inhibitors
Nomifensine
Norepinephrine Plasma Membrane Transport Proteins
Nicotinic Antagonists
Mecamylamine
Synaptosomes
Inhibitory Concentration 50
Norepinephrine

Keywords

  • Carrier mediated release
  • DMPP
  • Dopamine release
  • Monoamine transporter
  • Nicotinic acetylcholine receptor
  • Serotonin release

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Carrier-mediated release of monoamines induced by the nicotinic acetylcholine receptor agonist DMPP. / Szász, Bernadett K.; Mayer, Aliz; Zsilla, G.; Lendvai, Balázs; Vízi, E.; Kiss, János P.

In: Neuropharmacology, Vol. 49, No. 3, 09.2005, p. 400-409.

Research output: Contribution to journalArticle

Szász, Bernadett K. ; Mayer, Aliz ; Zsilla, G. ; Lendvai, Balázs ; Vízi, E. ; Kiss, János P. / Carrier-mediated release of monoamines induced by the nicotinic acetylcholine receptor agonist DMPP. In: Neuropharmacology. 2005 ; Vol. 49, No. 3. pp. 400-409.
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