EFFECTS OF ANTI-INFLAMMATORY AGENTS AND SOME OTHER DRUGS ON PROSTAGLANDIN BIO-TRANSPORT

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 198  (2) , 481-488
Abstract
The inhibitory effects of drugs on prostaglandin [PG] biotransport were studied by measuring the concentrative accumulation of 3H by rabbit choroid plexuses, segments of anterior uvea and kidney cortex slices after incubation in tissue culture medium containing 3H-PGF2.alpha.. After 10 min of incubation in the absence of an inhibitor, the choroid plexus showed a tissue/medium 3H accumulation ratio of 14 .+-. 0.7; after 30 min of incubation, the anterior uvea and the kidney cortex slices showed accumulation ratios of 6.4 .+-. 0.5 and 5.6 .+-. 0.1, respectively. The I50 [50% inhibition] values for inhibition of 3H accumulation by indomethacin were 10, 8 and 12 .mu.M for the 3 tissues, respectively. Some related drugs, oxyphenbutazone, D-naproxen, l-naproxen, ibuprofen, phenylbutazone and pirprofen, were effective inhibitors of 3H accumulation (I50 for anterior uvea, 6-28 .mu.M), whereas aspirin, dexamethasone phosphate and penicillin had an inhibitory effect only at much higher concentrations (I50 0.1-2.0 mM). Papaverine, fursemide and probenecid were approximately as effective as the anti-inflammatory organic acids (I50 0.01-0.1 mM), whereas bromcresol green was at least 10-fold more effective. Diphenhydramine and the nonacidic PG synthesis inhibitors, phenelzine and paracetamol, showed little (I50 > 1 mM) or no inhibitory effect. The inhibition of this transport system by some drugs, most notably nonsteroidal anti-inflammatory organic acids, and consequent alterations in the distribution and disposition of PG must be taken into account in the development of new anti-inflammatory agents and in the interpretation of the mechanism of action and side effects of such drugs.