Inhibition of neuronal nitric oxide synthase potentiates the dimethylphenylpiperazinium-evoked carrier-mediated release of noradrenaline from rat hippocampal slices.
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.
Kiss
J P
JP
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Sershen
H
H
Lajtha
A
A
Vizi
E S
ES
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology; D014316:Tritium
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D007191:Indazoles; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014316:Tritium; D009569:Nitric Oxide; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D009638:Norepinephrine