Comparative effects of several nitric oxide donors on intracellular cyclic GMP levels in bovine chromaffin cells: correlation with nitric oxide production
Article first published online: 29 JAN 2009
1999 Nature Publishing Group
British Journal of Pharmacology
Volume 127, Issue 3, pages 779–787, June 1999
How to Cite
Ferrero, R., Rodríguez-Pascual, F., Miras-Portugal, M. T. and Torres, M. (1999), Comparative effects of several nitric oxide donors on intracellular cyclic GMP levels in bovine chromaffin cells: correlation with nitric oxide production. British Journal of Pharmacology, 127: 779–787. doi: 10.1038/sj.bjp.0702607
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received July 27, 1998, Revised January 27, 1999, Accepted March 19, 1999)
- Cyclic GMP;
- nitric oxide donors;
- nitric oxide measurements;
- sodium nitroprusside
Sodium nitroprusside, S-nitroso-N-acetyl-D,L-penicillamine, Spermine NONOate and DEA NONOate raised cyclic GMP levels in bovine chromaffin cells in a time and concentration dependent manner with different potencies, the most potent being DEA/NO with an EC50 value of 0.38±0.02 μM.
Measurements of NO released from these donors revealed that DEA/NO decomposed with a half-life (t1/2) of 3.9±0.2 min. The t1/2 for SPER/NO was 37±3 min. SNAP decomposed more slowly (t1/2=37±4 h) and after 60 min the amount of NO produced corresponded to less than 2% of the total SNAP present. The rate of NO production from SNAP was increased by the presence of glutathione.
For DEA/NO and SPER/NO there was a clear correlation between nitric oxide production and cyclic GMP increases. Their threshold concentrations were 0.05 μM and maximal effective concentration between 2.5 and 5 μM.
For SNAP, threshold activation was seen at 1 μM, whereas full activation required a higher concentration (500–750 μM). The dose-response for SNAP increases in cyclic GMP was shifted nearly two orders of magnitude lower in the presence of glutathione. At higher concentrations an inhibition of cyclic GMP accumulation was found. This effect was not observed with either the nitric oxide-deficient SNAP analogue or other NO donors.
Although NO-donors are likely to be valuable for studying NO functions, their effective concentrations and the amount of NO released by them are very different and should be assessed in each system to ensure that physiological concentrations of NO are used.
British Journal of Pharmacology (1999) 127, 779–787; doi:10.1038/sj.bjp.0702607