K(+)-evoked [(3)H]-norepinephrine release in human brain slices from epileptic and non-epileptic patients is differentially modulated by gabapentin and pinacidil.
The modulation of K(+)-evoked [(3)H]-norepinephrine ([(3)H]-NE) release by gabapentin (GBP) and pinacidil (PIN), a known K(ATP) agonist, was examined in human brain slices. We compared the pharmacological effects on NE-release in human epileptic neocortex and epileptic hippocampus to non-epileptic neocortex. GBP (100 microM) decreased [(3)H]-NE release by 22% in non-epileptic neocortical slices, whereas this inhibition was absent in slices from epileptic hippocampus and epileptic neocortex. PIN (10 microM) also reduced [(3)H]-NE release by 30% in non-epileptic neocortical slices and only by 5% in epileptic hippocampal slices. The blockade of voltage-gated calcium channels by omega-conotoxins MVIIA and MVIIC (0.1 microM) reduced [(3)H]-NE release in epileptic and non-epileptic neocortical slices to the same extend. The data show a marked reduction in K(+)-evoked [(3)H]-NE release by GBP and PIN in epileptic hippocampus and neocortex, suggesting an alteration of K(ATP) channel function, whereas the effects of the calcium channel modulators omega-conotoxins MVIIA and MVIIC are similar in both epileptic and non-epileptic neocortex.
Freiman
Thomas M
TM
Department of Neurosurgery, Neurocentre, University Hospital, Albert-Ludwigs-University, Breisacher Strasse 64, D-7106 Freiburg im Breisgau, Germany. freiman@nz.ukl.uni-freiburg.de
Surges
Rainer
R
Kukolja
Juraj
J
Heinemeyer
Jan
J
Klar
Maximilian
M
van Velthoven
Vera
V
Zentner
Josef
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000588:Amines / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D000068438:Brimonidine Tartrate; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002648:Child; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004827:Epilepsy / Q000473:pathology*; D005260:Female; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*; D020960:omega-Conotoxins / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000588:Amines; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D003509:Cyclohexanecarboxylic Acids; D011810:Quinoxalines; D020960:omega-Conotoxins; D014316:Tritium; D000068438:Brimonidine Tartrate; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020110:Pinacidil; D011188:Potassium; D009638:Norepinephrine; D019329:Idazoxan