A possible role of nitric oxide in the regulation of dopamine transporter function in the striatum.
Brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) on striatal dopamine (DA) release in the anesthetized rat. Systemic administration of L-NAME (10 mg/kg, i.p.) significantly decreased the resting release of DA. The peak effect (23% decrease) was reached 45 min after injection. The inactive enantiomer D-NAME (10 mg/kg, i.p.) or the vehicle (saline, 5 ml/kg i.p.) had no effect on the striatal DA level. Neither treatment altered significantly the concentration of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). To investigate the possible involvement of the DA uptake system L-NAME was injected also in the presence of the DA uptake inhibitor nomifensine. Local application of nomifensine (10 microM in the dialysate medium) increased the extracellular concentration of DA to about eight-fold of the basal value and stabilized it at this higher level. Under these conditions L-NAME (10 mg/kg, i.p.) was not able to alter the striatal DA level. Neither nomifensine nor L-NAME caused any change in the level of DOPAC and HVA. Our data suggest that endogenously produced nitric oxide may influence the activity of the DA transporter which effect may have special importance in the regulation of extracellular transmitter concentration in the striatum.
Kiss
J P
JP
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Hennings
E C
EC
Zsilla
G
G
Vizi
E S
ES
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009627:Nomifensine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine