Abstract
1 The fate of (15S)-15-methyl prostaglandin E(2) methyl ester and 16,16-dimethyl prostaglandin E(2) in the pulmonary circulation of rat isolated lungs was compared with that of prostaglandin E(2) by means of bioassay.2 Calculated on the basis of height of response of the assay tissues, the inactivation of prostaglandin E(2) was 96 +/- 1%, of 15-methyl prostaglandin E(2) methyl ester, 53 +/- 6% and of 16,16-dimethyl prostaglandin E(2), 50 +/- 4%.3 Responses of the hamster stomach strip to the prostaglandin E(2) analogues passing through the pulmonary circulation were prolonged and slower in onset than those to the analogue given directly to the tissue. No such difference was observed with prostaglandin E(2).4 Bromocresol green, bromothymol blue, bromocresol purple and thymol blue (10(-5) M) all inhibited the inactivation of the three prostaglandins studied, as did diphloretin phosphate (1.5 x 10(-6) M). All five inhibitors also reversed the shape change in response seen after transpulmonary injection of 16-16-dimethyl prostaglandin E(2).5 We conclude that the inactivation of the methyl analogues is due to uptake, as they are not substrates for prostaglandin dehydrogenase.6 The lung may act as a depot for some compounds taking them up from the pulmonary vessels and later releasing them slowly into the systemic circulation.