Elsevier

Neuroscience Letters

Volume 215, Issue 2, 6 September 1996, Pages 115-118
Neuroscience Letters

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

https://doi.org/10.1016/0304-3940(96)12959-1Get rights and content

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 [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 Ca2+-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.

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    L-Arginine (100 μM), NO donors (SNP and SIN-1, 10 μM each), and cGMP derivatives (8-Br-cGMP, 300 μM) were reported to potentiate 3,4-diaminopyridine (200 μM)-evoked noradrenaline release in the rat hippocampal slices and synaptosomes, which was inhibited by either hemoglobin or the NOS inhibitor L-NA (10 μM) (Lauth et al., 1993, 1995). However, another study (Kiss et al., 1996) showed that the selective nNOS inhibitor 7-NI (40 μM) potentiated the dimethylphenylpiperazinium (20 μM)-evoked carrier-mediated release of noradrenaline from rat hippocampal slices. Studies on other brain regions have also revealed that NO could modulate the noradrenaline release.

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