Inhibition of neuronal nitric oxide synthase potentiates the dimethylphenylpiperazinium-evoked carrier-mediated release of noradrenaline from rat hippocampal slices

Neurosci Lett. 1996 Sep 6;215(2):115-8.


The effect of 7-nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS) on the dimethylphenylpiperazinium(DMPP)-evoked release of [3H]noradrenaline ([3H]NA) from rat hippocampal slices was studied. The effect of DMPP (20 microM) to increase the basal release of [3H]NA was significantly potentiated by 7-NI (40 microM). In our previous study we showed that the response to DMPP has two components, a nicotinic receptor-mediated, [Ca2+]-dependent exocytosis followed by a [Ca2+]-independent, uptake blocker-sensitive carrier-mediated release. To clarify which part of the response was affected by the inhibition of nNOS, we investigated the effect of 7-NI on the nicotine-evoked NA release (nicotine has only receptor-mediated effect) and on the DMPP-evoked NA release in Ca(2+)-free medium where the receptor-mediated component is abolished. Nicotine (100 microM) significantly increased the basal release of [3H]NA but this release was not affected, whereas in Ca(2+)-free medium the response to DMPP (20 microM) was still potentiated by 7-NI (40 microM). In the presence of the NA uptake blocker desipramine (10 microM) DMPP (20 microM) was unable to provoke NA release independently from the presence or absence of 7-NI (40 microM). Our data show that 7-NI influences the carrier-mediated component of DMPP-evoked [3H]NA release, which indicates that nitric oxide produced by nNOS may play a role in the regulation of the NA uptake carrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism
  • Dimethylphenylpiperazinium Iodide / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Indazoles / pharmacology
  • Male
  • Neurons / chemistry
  • Neurons / drug effects
  • Neurons / enzymology*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology*
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / metabolism
  • Norepinephrine / metabolism*
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / physiology
  • Tritium


  • Carrier Proteins
  • Enzyme Inhibitors
  • Indazoles
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Tritium
  • Nitric Oxide
  • Dimethylphenylpiperazinium Iodide
  • Nicotine
  • Nitric Oxide Synthase
  • 7-nitroindazole
  • Norepinephrine