PMID: 2492201Feb 9, 1989Paper

Weak inhibition of protein kinase C coupled with various non-specific effects make sphingosine an unsuitable tool in platelet signal transduction studies

Biochimica Et Biophysica Acta
S KrishnamurthiV V Kakkar

Abstract

The effects of sphingosine, the newly described inhibitor of the enzyme protein kinase C, on human platelet activation, were studied in order to gain further information on the role of protein kinase in platelet responses. Concentrations of the drug (5-20 microM) which had little effect on protein kinase C activation as measured by the phosphorylation of the 45 kDa and 20 kDa protein substrates induced by phorbol 12-myristate 13-acetate (PMA) and thrombin, strongly inhibited platelet aggregation induced by these agonists, as well as aggregation induced by ADP and ionomycin, which caused no detectable protein kinase C activation or 5-hydroxy[14C]tryptamine[( 14C]5HT) secretion. At approx. 10-fold higher concentrations (150-200 microM), sphingosine had significant inhibitory effects on PMA and thrombin-induced 45 kDa and 20 kDa protein phosphorylation. However, at these high concentrations, the drug caused extensive membrane damage/leakiness as suggested by the substantial release of [14C]5HT and [3H]adenine from pre-loaded platelets (50-70% release of both markers), and the total quenching of quin2 fluorescence by Mn2+ in the presence of the drug. Due to the increased membrane leakiness in the presence of the drug, an apparent p...Continue Reading

References

Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·G B ZavoicoM B Feinstein
Mar 13, 1986·Biochemical and Biophysical Research Communications·T TamaokiF Tomita
Jun 1, 1984·The Biochemical Journal·M J Berridge

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Citations

Jul 10, 1999·Amino Acids·V Constantinou-Kokotou, G Kokotos
Nov 30, 1992·Chemico-biological Interactions·J H Mäkelä, B Isomaa
Oct 1, 1989·Trends in Pharmacological Sciences·S Joseph, S Krishnamurthi

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