4-Aminopyridine stimulates B-50 (GAP43) phosphorylation and [3H]noradrenaline release in rat hippocampal slices.
In situ phosphorylation of the presynaptic protein kinase C substrate B-50 was investigated in rat hippocampal slices incubated with the convulsant drug 4-aminopyridine (4-AP). Phosphorylation of B-50 was significantly enhanced 1 min after the addition of 4-AP (100 microM). This increase by 4-AP was concentration dependent (estimated EC50 30-50 microM). Concomitant with the changes in B-50 phosphorylation, 4-AP also dose-dependently stimulated [3H]noradrenaline [( 3H]NA) release from the slices. 4-AP stimulated [3H]NA release within 5 min to seven times the control level. The B-50 phosphorylation induced by 4-AP remained elevated after removal of the convulsant, this is contrast to B-50 phosphorylation induced by depolarization with K+. A similar persistent increase was observed for [3H]NA release after a 5-min incubation period with 4-AP. These results give more insight into the molecular mechanisms underlying 4-AP-induced epileptogenesis and provide further evidence for the correlation between B-50 phosphorylation and neurotransmitter release in the hippocampal slice.
Heemskerk
F M
FM
Division of Molecular Neurobiology, Rudolf Magnus Institute, University of Utrecht, The Netherlands.
Schrama
L H
LH
Gianotti
C
C
Spierenburg
H
H
Versteeg
D H
DH
De Graan
P N
PN
Gispen
W H
WH
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein; D006133:Growth Substances / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009994:Osmolar Concentration; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D019922:GAP-43 Protein; D006133:Growth Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014316:Tritium; D015761:4-Aminopyridine; D011188:Potassium; D009638:Norepinephrine