| Popis: |
Indomethacin, fenoprofen, naproxen, acetylsalicylic acid, phenylbutazone and sulfinpyrazone were studied as inhibitors of serotonin release and of cyclooxygenase activity in human platelets. Inhibition by indomethacin, acetylsalicylic acid and naproxen, but not the other drugs, was time-dependent and irreversible. When release of serotonin-14C was induced by dilute collagen all drugs produced concentration-dependent inhibition which became virtually complete at higher drug concentrations. The rank order of potency of the inhibitors was similar to that observed for cyclooxygenase activity of washed platelets for most drugs. These observations indicate the importance of arachidonate metabolism as the principal pathway mediating the action of dilute collagen. Acetylsalicylic acid which is relatively loosely bound to albumin inhibited release in plasma and enzyme activity in washed platelets with approximately equal potency. The other drugs are more avidly bound to albumin, and concentrations required to inhibit release were 10 to 50 times greater than the concentrations which produced a similar degree of inhibition of cyclooxygenase activity in the washed platelet system. The potency of the drugs was compared with their potency as inhibitors of cyclooxygenase activity of gastric mucosa. The effect of fenoprofen and of sulfinpyrazone was considerably stronger in the platelet system, while the other drugs exhibited activity which was comparable on the 2 tissues. |
