Released adenosine diphosphate stabilizes thrombin-induced human platelet aggregates.

نویسندگان

  • M Cattaneo
  • M T Canciani
  • A Lecchi
  • R L Kinlough-Rathbone
  • M A Packham
  • P M Mannucci
  • J F Mustard
چکیده

Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, chymotrypsin, and prostaglandin E1 (PGE1). In contrast, thrombin-induced aggregates of platelets from patients with delta-storage pool deficiency (delta-SPD), which lack releasable nucleotides, are readily deaggregated by the same combination of inhibitors. The ease with which delta-SPD platelets are deaggregated is caused by the lack of stabilizing effects of released ADP, since: (1) exogenous adenosine diphosphate (ADP) (10 mumol/L), but not serotonin (2 mumol/L), abolishes the ability of these inhibitors to deaggregate delta-SPD platelets; (2) thrombin-induced aggregates of platelets from a patient (V.R.) (whose platelets have a severe, selective impairment of sensitivity to ADP, but normal amounts of releasable nucleotides) can be readily deaggregated, and addition of ADP does not stabilize the platelet aggregates; (3) apyrase or creatine phosphate (CP)/creatine phosphokinase (CPK), added before thrombin, make control platelets more easily deaggregated by hirudin, chymotrypsin, and PGE1, and do not change the deaggregation response of delta-SPD platelets and of V.R.'s platelets. Thrombin-induced aggregation and release of beta-thromboglobulin in control, delta-SPD, and in V.R.'s platelets was similar and not inhibited by apyrase or CP/CPK. The stabilizing effect of ADP on platelet aggregates is specific, since epinephrine in the presence of apyrase to remove traces of released ADP does not stabilize the aggregates of control, delta-SPD, or of V.R.'s platelets. Because epinephrine increases fibrinogen binding to thrombin-stimulated platelets to a greater extent than ADP, but does not stabilize the aggregates, it is unlikely that the additional fibrinogen binding sites induced by ADP have a major role in inhibiting deaggregation by the combination of inhibitors.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Fibrinogen-independent aggregation and deaggregation of human platelets: studies in two afibrinogenemic patients.

Platelets from two afibrinogenemic patients were used to determine whether fibrinogen is essential for platelet aggregation and to examine whether released fibrinogen contributes to the stabilization of platelet aggregates when platelets have been induced to aggregate and release their granule contents by stimulation with thrombin. The addition of adenosine diphosphate (ADP) to platelet-rich pl...

متن کامل

Heterogeneity of human platelets. II. Functional evidence suggestive of young and old platelets.

In the previous communication, suggestive evidence was presented for large-heavy platelets being "young" platelets and light-small platelets being "old" platelets. Large-heavy, light-small, and total human platelet populations were compared with respect to their platelet function. After addition of adenosine diphosphate (ADP), thrombin, or epinephrine, platelet aggregation time was 3.0-, 4.5-, ...

متن کامل

Arachidonate-induced fibrinogen binding to thrombin-degranulated rabbit platelets is independent of released ADP.

It has been established that fibrinogen binding occurs during adenosine diphosphate (ADP)-induced platelet aggregation. but studies of fibrinogen binding to platelets stimulated with arachidonate or most other aggregating agents are complicated by the release of platelet granule contents. which include both ADP and fibrinogen. Therefore. thrombin-degranulated rabbit platelets that have released...

متن کامل

Effect of the Enzymatic Removal of ADP on the Binding of Fibrinogen to Thrombin or ADP - Stimulated Platelets

Thrombin and adenosine diphosphate (ADP) supported the binding of 125l-fibrinogen to washed human platelets with similar kinetics and affinity. Platelet secretion, as measured by 14C-serotonin release, and fibrinogen binding exhibited an identical dependence on thrombin concentration. Enzymatic removal of ADP with apyrase or creatine phosphate/creatine phosphokinase (CP/CPK) from thrombin-stimu...

متن کامل

Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation/aggregation induced by sera from heparin-induced thrombocytopenia patients.

The molecular basis for heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, is not yet fully understood. We found that pretreatment of platelets with AR-C66096 (formerly FPL 66096), a specific platelet adenosine diphosphate (ADP) receptor antagonist, at a concentration of 100 to 200 nmol/L that blocked ADP-dependent platelet aggregation, resulted in comp...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Blood

دوره 75 5  شماره 

صفحات  -

تاریخ انتشار 1990