Staurosporine-independent platelet aggregation induced by the calcium ionophore ionomycin is inhibited by prostacyclin and sodium nitroprusside and stimulated by adrenaline.
Preincubation of platelets with the protein kinase inhibitor staurosporine is known to abolish the calcium ionophore-induced ATP secretion but to decrease aggregation only partially. This indicates that, while exocytosis is necessarily connected to protein phosphorylation, a Ca(2+)-dependent aggregation occurs independently of protein phosphorylation. This aggregation pathway was inhibited by prostacyclin and sodium nitroprusside, which increase the endogenous synthesis of cyclic AMP and cyclic GMP, respectively. The effect of the cyclic nucleotides was linked to the protein phosphorylation induced by them. The staurosporine-insensitive aggregation was strongly potentiated by adrenaline, an alpha 2-adrenergic agonist; adrenaline also counteracted the inhibition induced by prostacyclin and nitroprusside, with no appreciable effect on the cAMP levels and on the cyclic nucleotide-dependent protein phosphorylation. Its effect was reversed by the alpha 2-antagonist yohimbine.
Doni
M G
MG
Institute of Human Physiology, Faculty of Medicine and Surgery, University of Padova, Italy.
Alexandre
A
A
Padoin
E
E
Francesconi
M A
MA
Deana
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010750:Phosphoproteins / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine; D015016:Yohimbine / Q000494:pharmacology
D000470:Alkaloids; D010750:Phosphoproteins; D009599:Nitroprusside; D015016:Yohimbine; D015759:Ionomycin; D003994:Bucladesine; D011464:Epoprostenol; D011493:Protein Kinase C; D006152:Cyclic GMP; D019311:Staurosporine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine