Inhibition of potassium-stimulated dopamine release by the nitric oxide generator isosorbide dinitrate.
In PC12 cells, isosorbide dinitrate (ISDN) and S-nitrosol-acetyl-penicillamine (SNAP), both nitric oxide (NO) generators, attenuated K+ (56 mM)-stimulated release of dopamine. The attenuation was not observed with isosorbide, an ISDN analog lacking NO generating capacity. In this model, A23187 (Ca2+ ionophore), Bay K8644 (Ca2+ slow channel agonist) and veratridine (Na+ channel agonist) stimulated dopamine release. Treatment with ISDN enhanced Bay K8644 and veratridine-evoked dopamine release, while ISDN had no significant effect on the A23187 response. Incubation with 8-bromo-cGMP (membrane permeable cGMP analog) had no effect on basal or stimulated dopamine release in these cells, suggesting NO's response was not mediated by cGMP. In additional studies, K+ (56 mM), Bay K8644 and veratridine elevated cytosolic free calcium levels ([Ca2+]i). ISDN reduced K(+)-stimulated increase in [Ca2+]i, but enhanced the increases of [Ca2+]i induced by Bay K8644 or veratridine. These results suggest NO interacts with K(+)-induced membrane depolarization (possibly by inhibiting membrane conductance to K+) to attenuate Ca2+ influx and Ca(2+)-mediated dopamine secretion stimulated by K+.
Sun
P
P
Department of Pharmacology and Toxicology, Purdue University, West Lafayette, IN 47907-1334, USA.
Kanthasamy
A
A
Yim
G K
GK
Isom
G E
GE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D016716:PC12 Cells; D017680:Potassium Compounds / Q000494:pharmacology*; D051381:Rats
D017680:Potassium Compounds; D009569:Nitric Oxide; D000001:Calcimycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007548:Isosorbide Dinitrate; D002118:Calcium; D004298:Dopamine