PMID: 7542370Feb 1, 1995Paper

Inhibition of potassium-stimulated dopamine release by the nitric oxide generator isosorbide dinitrate

Neuropharmacology
P SunG E Isom

Abstract

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+.

References

Apr 1, 1992·Neuron·O ManzoniL Fagni
May 27, 1992·European Journal of Pharmacology·H Prast, A Philippu
Sep 22, 1992·European Journal of Pharmacology·G LonartK M Johnson
Sep 1, 1992·Scientific American·E R Kandel, R D Hawkins
Sep 1, 1991·Toxicology and Applied Pharmacology·A G KanthasamyG E Isom
Oct 12, 1993·European Journal of Pharmacology·C Chen, G G Schofield

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Citations

Jan 9, 1998·Progress in Neurobiology·J Myslivecek
Jul 13, 1999·Journal of Endocrinological Investigation·L PinillaE Aguilar

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