Effect of nitric oxide donors on endogenous dopamine release from rat striatal slices - II: The role of voltage-dependent sodium channels, calcium channel activation, reverse transport mechanism, guanylate cyclase and endogenous glutamate


Buyukuysal R. L.

FUNDAMENTAL & CLINICAL PHARMACOLOGY, vol.11, no.6, pp.528-536, 1997 (SCI-Expanded) identifier identifier identifier

Abstract

Incubation of striatal slices with sodium nitroprusside (SNP) or hydroxylamine (HA) for 60 min caused a dose-dependent increase in dopamine (DA) release. This effect was inhibited completely by tetrodotoxin (TTX) (1 mu M) if low concentrations of SNP (1 mu M) or HA (10 and 100 mu M) were tested. Although higher concentration of SNP (10 and 100 mu M) and HA (500 mu M) were still effective in stimulating DA release, increases observed under these conditions were less than the values found in the absence of TTX. Verapamil (10 mu M), but not omega-conotoxin (100 mu M), significantly reduced DA release stimulated by high concentrations of SNP or HA. When verapamil was combined with TTX, moreover, SNP and HA failed to stimulate DA release. If striatal slices were incubated in the presence of nomifensine (10 mu M), SNP and HA did not enhance DA release. SNP and HA-induced depletions in tissue DA levels were also protected by nomifensine. Inhibition of guanylate cyclase with 10 mu M of methylene blue could not reduce the effects of NO-donors. SNP and HA also failed to alter endogenous glutamate release from striatal slices. Similarly, SNP and HA-induced increases in DA release were not affected by kynurenic acid and MK-801. These results indicate that NO-donors SNP and HA stimulate DA release by facilitating reverse DA transport. ?his effect seems to be dependent on the activation of both voltage dependent sodium channels and L-type of calcium channels. Results presented here also indicate that neither endogenous glutamate nor guanylate cyclase activation plays an intermediary role in stimulatory effects of NO-donors on DA release from rat striatal slices.