Chapter 19. Modulation of the Arachidonic Acid Cascade

Abstract

Publisher Summary Prostaglandins are biosynthesized from arachidonic acid. Arachidonic acid serves as a precursor for a virtual cascade of acidic lipids, each possessing distinct and profound pharmacological activities. Prostacycline (PGX) is both a potent inhibitor of platelet aggregation and an arterial vasodilator. The endoperoxides decompose into the fatty acid HHT. This transformation is probably a non-enzymatic artifact and no biological activity. Another fatty acid, HETE, formed from arachidonic acid by a platelet lipoxygenase has been found to exhibit chemotactic activity for neutrophils and eosinophils. Agonists design to exploit the potential therapeutic uses of the prostaglandins. Prostaglandin activities are to modulate the enzymes that control the tissue levels. Anti-inflammatory steroids exhibit potent inhibitory effects on prostaglandin production in rheumatoid synovial. Bradykinin releases prostaglandins from phospholipid in a variety of systems, an effect thought to augment the activities of this peptide. The local anaesthetic tetracaine and psychotropic drug meprobamates are reported to inhibit prostaglandin biosynthesis at the phospholipase level. Non-steroidal anti-inflammatory (NSAI) agents owe their pharmacological activity to the inhibition of prostaglandin biosynthesis (PGBS). Both aspirin and dexamethasone depress the acute inflammatory response to carrageenin in rats. Deplete of arachidonic acid suggests that the activities other than PGBS inhibition contribute to the anti-inflammatory effects of both steroids and NSAl agents. Inhibition of PGBS by a series of NSAl agents appear to be better correlated with the analgesic effects than with the anti-inflammatory activity.