Differential effect of acetylsalicylic acid and dipyrone on prostaglandin production in human fibroblast cultures

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Abstract
Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins [PG]. They produce the same PG after stimulation with bradykinin. Basal release of PGI2 (6-oxo-PGF1.alpha.), F2.alpha. and E2 is inhibited dose-dependently by both acetylsalicylic acid (ASA) and dipyrone (P < 0.05). The examined dose-range was 10-7-10-4 M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin-stimulated release remains dose-dependently inhibited (P < 0.001) in ASA-, but not in dipyrone-treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P < 0.0001), whereas the dipyrone-treated cultures are not different from controls. The findings are consistent with cyclooxygenase inhibition by ASA as well as by dipyrone. The data demonstrate rapid reversibility of the effect of dipyrone. Evidently in contrast to ASA, dipyrone does not inhibit cyclooxygenase by binding covalently to the enzyme.