4-Aminopyridine Stimulates B-50 (GAP43) Phosphorylation and [3H]Noradrenaline Release in Rat Hippocampal Slices

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Abstract
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 .mu.M). This increase by 4-AP was concentration dependent (estimated EC50 30-50 .mu.M). 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 in 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.

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