Attenuation of alkalizing effect of thrombin by S-nitrosoglutathione in human platelets.
S-Nitrosoglutathione and sodium nitroprusside, two activators of the soluble guanylate cyclase, inhibit the intracellular calcium rise evoked by thrombin at an early step of the activation cascade. A similar effect is obtained with prostaglandin E1, a drug that increases cAMP. We have found that in human platelets thrombin 0.1 IU/ml (approximately 1 nmol/l) produced a transient increase of [Ca2+]i. After a 10-min preincubation at 37 degrees C in 100 mumol/l S-nitrosoglutathione the peak value was reduced by 79 +/- 4% (mean and SEM, percentage of the parallel control). The [Ca2+]i peak was reduced by 66 +/- 4% after preincubation in 100 mumol/l sodium nitroprusside, and by 90 +/- 2% after preincubation in 10 mumol/l prostaglandin E1. Thrombin has a slow alkalizing effect. After a 10-min preincubation at 37 degrees C in 100 mumol/l S-nitrosoglutathione the change in pHi produced by thrombin was reduced by 35 +/- 5%, but only 12 +/- 4% after preincubation in 100 mumol/l sodium nitroprusside. The alkalizing effect of thrombin was also blunted by 10 mumol/l prostaglandin E1: the change of intracellular pH was decreased by 39 +/- 5%. As a conclusion, these drugs in addition to the reduction of rise in [Ca2+]i have an inhibitory effect on the alkalizing response induced by thrombin.
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina. cicme@atlas.med.unlp.edu.ar
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D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007700:Kinetics; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D026422:S-Nitrosoglutathione; D013917:Thrombin / Q000494:pharmacology*
D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D009599:Nitroprusside; D026422:S-Nitrosoglutathione; D013917:Thrombin; D000527:Alprostadil; D005978:Glutathione; D002118:Calcium