Characterisation of GEA 3175 on human platelets;: comparison with S-nitroso- N-acetyl-D,L-penicillamine

By comparing the effect of two nitric oxide (NO)-containing compounds, we found that S-nitroso- N-acetyl- d, l-penicillamine (SNAP), but not GEA 3175 (1,2,3,4-Oxatriazolium,3-(3-chloro-2-metylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt), released NO. Despite this, both drugs elevated cyclic guanosine 3′,5′-monophosphate (cGMP) levels in human platelets. However, SNAP was more effective after short exposure times (5 and 20 s). The compounds also inhibited thrombin-induced rises in cytosolic Ca 2+. Time studies revealed that the action of SNAP rapidly declined by increasing the length of incubation (from 5 s to 30 min). This desensibilisation phenomenon mainly involved the release of Ca 2+ from intracellular stores. In comparison, GEA 3175-induced inhibition of cytosolic Ca 2+ signalling was much more long-lasting. The soluble guanylyl cyclase (sGC) inhibitor 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ) reversed the effect of GEA 3175 on cytosolic Ca 2+. Consequently, this inhibition depends solely on the increase in cGMP. In summary, differences between GEA 3175 and SNAP were observed in NO releasing, cGMP elevating and Ca 2+ suppressive properties.