Selegiline induces dopamine release through ATP-sensitive potassium channels in the rat caudate-putamen in vitro.
We used superfusion chambers to investigate the role of ATP-sensitive potassium (KATP) channels in dopamine (DA) release elicited by the monoamine oxidase inhibitor selegiline in the rat caudate-putamen in vitro. Selegiline (R[-]-deprenyl], but not the S[+] enantiomer, concentration-dependently induced increases in extracellular concentrations of DA, with a maximal increase to 185% in comparison to basal outflow at 0.1 mM selegiline. Since in our experimental conditions exclusive MAO inhibition does not lead to an enhancement of extracellular DA levels, the effect of selegiline on DA levels seems not to be related to MAO inhibition. Butanedione (0.1 mM), a specific KATP channel blocker, also significantly enhanced extracellular DA levels in the rat caudate-putamen to approx. 260%. Selegiline only led to an additional increase of DA outflow, when added to submaximal concentrations of butanedione or tolbutamide, implying that selegiline is acting on identical sites. When the KATP channel opener cromakalim was added to the incubation medium, basal as well as butanedione-enhanced DA levels markedly decreased to about 40% when compared to baseline values. Selegiline-activated DA release was also antagonized by cromakalim. The selegiline effect was neither modulated by preincubation with the uptake inhibitor nomifensine nor by the DA agonist quinpirole and antagonist sulpiride. In conclusion these results suggest that selegiline is able to modulate KATP channels in the caudate-putamen of the rat in vitro resulting in an enhancement of striatal DA release.
Neusch
C
C
Department of Neurology, Medical University of Lübeck, Germany.
Schnierle
S
S
Moser
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D015221:Potassium Channels; D012642:Selegiline; D000255:Adenosine Triphosphate; D004298:Dopamine