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

Abstract

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 μM) to increase the basal release of [3H]NA was significantly potentiated by 7-NI (40 μM). In our previous study we showed that the response to DMPP has two components, a nicotinic receptor-mediated, [Ca 2+]-dependent exocytosis followed by a [Ca 2+]-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 μM) significantly increased the basal release of [ 3H]NA but this release was not affected, whereas in Ca2+-free medium the response to DMPP (20 μM) was still potentiated by 7-NI (40 μM). In the presence of the NA uptake blocker desipramine (10 AM) DMPP (20 μM) was unable to provoke NA release independently from the presence or absence of 7-NI (40 μM). 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.