External Ca(2+)-independent norepinephrine release from hippocampal slices and modulation by protein kinase C activation.

4 beta-Phorbol 12,13-dibutyrate (PDB) enhanced [3H] norepinephrine ([3H]NE) release from rat hippocampal slices evoked by 3,4-diaminopyridine (3,4-DAP, 100-400 mumol.L-1), veratridine (1-7 mumol.L-1) or ouabain (100-200 mumol.L-1), but had no effect on those evoked by monensin (0.01-10 mumol.L-1) in the absence of extracellular Ca2+. Tetrodotoxin (TTX, 0.3 mumol.L-1) blocked [3H]NE release evoked by 3,4-DAP, veratridine, or ouabain, but failed to affect that evoked by monensin. Tetraacetoxy methyl ester of 1-2-bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), Ca2+ chelator, inhibited the [3H]NE release evoked by these substances, but did not inhibit the enhancement of the evoked NE release by PDB. The findings suggest that under external Ca(2+)-free conditions protein kinase C activation enhances [3H]NE release evoked by the membrane depolarizing agents, but does not affect that evoked by Na(+)-induced internal Ca2+ release.