Effect of sulphasalazine on pulmonary inactivation of prostaglandin F2 alpha in the pig.
1 The metabolism of prostaglandin F2 alpha (PGF2 alpha) 15 nm in 100,000 g supernatant fractions from piglet lung homogenates was inhibited by sulphasalazine with an IC50 value of 25 micrometers. 2 The piglet isolated lung perfused with Krebs solution, containing either albumin or Ficoll 70 to prevent oedema and vascular damage, efficiently metabolized PGF2 alpha given as a bolus injection (1 ng in 0.1 ml; 30 nm). 3 In Krebs solution containing Ficoll 70, sulphasalazine inhibited the pulmonary inactivation of PGF2 alpha in a dose-dependent manner with an IC50 value of 110 micrometers. No inhibition of inactivation by sulphasalazine was found when the perfusion fluid contained albumin, which is known to bind this drug effectively. 4 Analysis of the separated efflux profiles for PGF2 alpha and its metabolites with reference to the dilution curve for an extracellular marker provided evidence that sulphasalazine inhibited PGF2 alpha uptake into lung cells. 5 We conclude that the effect of sulphasalazine on pulmonary prostaglandin inactivation is primarily due to inhibition of prostaglandin transport, and not to inhibition of prostaglandin metabolism.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002474:Cell-Free System; D003911:Dextrans / Q000494:pharmacology; D015237:Dinoprost; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology*; D013552:Swine
D003911:Dextrans; D011460:Prostaglandins F; D012460:Sulfasalazine; D015237:Dinoprost