Iloprost antagonizes the increase in internal calcium concentration induced by alpha-thrombin in human platelets: a study of desensitization.
Cardiovasc Drugs Ther
; 9(6): 773-7, 1995 Dec.
Article
in En
| MEDLINE
| ID: mdl-8850381
ABSTRACT
We studied the interaction between the synthetic prostacyclin analog iloprost and the aggregating agent alpha-thrombin by measuring the internal calcium ion concentration ([Ca(2+)]i) of human fura-2-loaded platelets. Iloprost (0.003-100 micrograms/l) did not modify the resting calcium level; when added 2 minutes before exposure of the platelets to a submaximally active concentration of alpha-thrombin (10 U/l), iloprost dose-dependently antagonized the increase in [Ca(2+)]i. To evaluate if iloprost retained this antagonistic effect even after a prolonged contact, which is well known to cause a "desensitization" phenomenon, platelets were preincubated with iloprost (35 micrograms/l) for 3 hours. After washout, the effect of newly added iloprost (0.01-100 micrograms/l) on the alpha-thrombin-induced increase in [Ca(2+)]i was tested. Iloprost was still able to antagonize the increase in [Ca(2+)]i induced by alpha-thrombin in "desensitized" platelets; however, the dose-inhibitory response curve was significantly shifted to the right when compared with that obtained in control platelets (i.e., platelets preincubated for 3 hours with iloprost's solvent), and the resulting IC50 was significantly higher 1.78 versus 0.2 micrograms/l (p < 0.001). Since the maximal inhibitory effect of iloprost could also be reached under these experimental conditions, we conclude that iloprost retains its ability to antagonize the increase in [Ca(2+)]i induced by alpha-thrombin in desensitized platelets.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Platelets
/
Platelet Aggregation Inhibitors
/
Thrombin
/
Calcium
/
Iloprost
Limits:
Humans
Language:
En
Journal:
Cardiovasc Drugs Ther
Year:
1995
Document type:
Article