[3,4-Diaminopyridine and 4-aminopyridine evoked neurotransmitter release

We used 3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP) as stimuli for evoking [3H]norepinephrine ([3H]NE) release in rabbit hippocampal slices to investigate the mechanism underlying the aminopyridines evoked [3H]NE release and the effect of protein kinase C activator phorbol ester PDB. 3,4-DAP and 4-AP evoked [3H]NE release were concentration dependent and enhanced by phorbol ester PDB. 4-AP (300 mumol.L-1) evoked [3H]NE release and enhancement of this evoked release by PDB were antagonized by protein kinase C inhibitor polymyxin B and almost abolished by tetrodotoxin. N-ethylmaleimide inhibited the facilitatory effect of PDB on 3,4-DAP evoked [3H]NE release implicating that G-protein is involved in the modulation of evoked [3H]NE release. 3,4-DAP evoked also dopamine release in caudate nucleus, and acetylcholine release in hippocampus suggesting that the mechanism by which 3,4-DAP evoked transmitters release is similar to that of electrical stimulation.