[Iptakalim enhances astrocytic glutamate uptake activity].
OBJECTIVE
To investigate the effect of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KATPCO), on astrocyte glutamate uptake activity. The mechanism of action involved was also examined.


METHODS
Primary cultures of astrocytes were prepared from cerebral cortexes of 1 to 2 days old Sprague-Dawley rats. Cultures were preincubated with iptakalim of various concentrations with the absence or presence of 6-hydroxydopamine (6-OHDA, 50 micromol x L(-1)). Then, the cells were treated with pinacidil (10 micromol x L(-1), K+ channel opener) instead of iptakalim and pretreated with glibenclamide (20 micromol x L(-1), ATP-sensitive K+ channel inhibitor) before pinacidil or iptakalim was added into the medium so that the mechanism of action of iptakalim could be analysed. Astrocyte glutamate uptake activity was determined by intracellular concentration of 3H labeled D,L-glutamate, using isotope techniques.


RESULTS
Both iptakalim and pinacidil were shown to increase glutamate uptake activity of astrocytes and reverse inhibitory effect induced by 6-OHDA. But the increased and reversed effects of iptakalim or pinacidil on astrocytic glutamate uptake were found to be completely antagonized by glibenclamide.


CONCLUSIONS
These data indicated that iptakalim can enhance astrocytic glutamate uptake activity due to its K+ channel opening properties and lessen glutamate excitotoxicity. Iptakalim may be useful for the therapy of Parkinson's disease.
Zhang
Yun
Y
Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, China.
Hu
Gang
G
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005971:Glutamates / Q000378:metabolism*; D005905:Glyburide / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000037:antagonists & inhibitors; D020110:Pinacidil / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D005971:Glutamates; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D018696:Neuroprotective Agents; D011437:Propylamines; D014665:Vasodilator Agents; D020110:Pinacidil; D016627:Oxidopamine; D005905:Glyburide