Effect of recombinant hirudin on cytosolic Ca2+ concentrations using different platelet stimulators.
Cytosolic Ca2+ concentration, [Ca2+]i, and aggregation behavior of hirudinized platelet suspensions were examined under stimulation with thrombin, adenosine diphosphate, platelet-activating factor, collagen and the calcium ionophore, ionomycin. A rise in [Ca2+]i, a key step in platelet activation, was only inhibited by recombinant hirudin r-hirudin using the agonist thrombin. All other stimulators including ionomycin were not affected by r-hirudin. If hirudinized blood was gel-filtered before platelet stimulation, thrombin induced the same response as citrated platelet suspensions. Aggregation studies and calcium influx using various stimulators showed good correlation: only thrombin-induced aggregation was completely inhibited by r-hirudin. These results support the hypothesis that hirudin inhibits platelet function by thrombin binding and not by direct interaction with platelets.
Kirchmaier
C M
CM
Department of Internal Medicine, J.W. Goethe University, Frankfurt, FRG.
Bellinger
O K
OK
Schulz
B
B
Breddin
H K
HK
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects*; D002118:Calcium / Q000032:analysis*; D002850:Chromatography, Gel; D003094:Collagen / Q000494:pharmacology; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006629:Hirudins; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D015759:Ionomycin; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D002118:Calcium; C060225:desirudin