The antiprostaglandin action of aspirin due to the acetylation of the enzyme prostaglandin synthetase is manifested by inhibition of the so-called release reaction and consequent abolition of secondary-phase aggregation. The maleic anhydrides, a series of reversible acylating agents, have now been shown to produce the aspirin-type defect in platelet aggregation. The antiplatelet effect of aspirin is irreversible. With 2,3-dimethylmaleic anhydride, however, the antiplatelet effect disappeared in approximately 80 min at 25°. Hence the persistence of the lesion when caused by aspirin results from the stability of the acetyl linkage formed in its reaction with prostaglandin synthetase. This suggests that the modification occurs at either a lysine or an NH 2-terminal amino group. That such is the case was confirmed by the observation that 3,4,5,6-tetrahydrophthalic anhydride and 2,3-dimethylmaleic anhydride, both amino-specific acylating agents, were able to effect the aspirin-type lesion. Thus, upon deacylation, prostaglandin synthetase regains its activity and platelet function returns to normal. Accordingly, it may be possible to develop a clinically acceptable, reversible acylating agent with short-acting, aspirin-like effects.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Dec 1 1977|
ASJC Scopus subject areas
- Molecular Medicine