Abstract
Previous studies have shown that, at concentrations of 1 μM and 10 μM, HP 749 increased electrically-stimulated release of [3H]norepinephrine (NE) from rat cortical slices. These effects were Ca2+-dependent, indicating an effect on release from vesicular stores. At 100 μM, HP 749 had two effects. In addition to enhancing the Ca2+-dependent electrically-evoked release, it also induced a rise in the basal efflux (spontaneous release) of [3H]NE, which was observed in both cortical slices and synaptosomes. The spontaneous release effect was (1) not blocked by the reuptake inhibitor nomifensine, (2) not affected by removal of external calcium, (3) not blocked by vesicular depletion with reserpine, and (4) not inhibited by the sodium channel blocker tetrodotoxin (TTX). As would be expected, the spontaneous [3H]NE release induced by the cytoplasmic releaser tyramine and the sodium channel activator veratridine were blocked by nomifensine and TTX, respectively. Notably, however, the Ca2+-independent veratridine-induced release was completely blocked by 100 μM HP 749. The mechanism of spontaneous release of [3H]NE caused by 100 μM HP 749 is unresolved at present; however, the data are consistent with this release originating from a cytoplasmic source.
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Smith, C.P., Huger, F.P., Petko, W. et al. HP 749 enhances calcium-independent release of [3H]norepinephrine from rat cortical slices and synaptosomes. Neurochem Res 19, 1265–1270 (1994). https://doi.org/10.1007/BF01006816
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DOI: https://doi.org/10.1007/BF01006816