RT Journal Article
SR Electronic
T1 ACETYLSALICYLIC ACID: INHIBITION OF PLATELET AGGREGATION IN THE RABBIT
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 410
OP 418
VO 179
IS 2
A1 F. J. ROSENBERG
A1 P. E. GIMBER-PHILLIPS
A1 G. E. GROBLEWSKI
A1 C. DAVISON
A1 D. K. PHILLIPS
A1 S. J. GORALNICK
A1 E. D. CAHILL
YR 1971
UL http://jpet.aspetjournals.org/content/179/2/410.abstract
AB Acetylsalicylic acid (ASA) inhibits the aggregation of platelets induced by collagen in rabbit plasma enriched with platelets. Extent of the inhibition is related both to incubation time and concentration of ASA. Salicylic acid is 50 to 100 times less potent than ASA, and inhibition by salicylic acid is independent of incubation time. Repeated washing and resuspension of the platelets after incubation with ASA does not reverse the ASA effect, whereas salicylic acid inhibition is abolished by washing. ASA inhibition of aggregation is related to acetylation of the platelet, a process different from acetate uptake. These two processes can be differentiated in three ways. 1) Platelet suspensions incubated with 3H-NaAc take up large quantities of acetate, but their ability to aggregate is unaffected. 2) Studies of lipid and protein distributions in platelets incubated with either 3H-acetyl ASA or 3H-NaAc demonstrate that 3H-acetyl ASA labels protein to a significantly greater degree than does 3H-NaAc, whereas 3H-NaAc labels the lipid fraction more extensively than does 3H-acetyl ASA. 3) Acetate uptake, but not protein acetylation, is blocked by addition of tetramethyleneglutaic anhydride to the incubate. Only 10% of the total platelet acetylation can be accounted for by a plasma intermediary. It is concluded that acetylsalicylic acid acetylates platelets directly and that this acetylation is related to inhibition of platelet aggregation. ASA inhibits platelet aggregation when given in vivo as well as in vitro. © 1971 by The Williams & Wilkins Co.