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UPTAKE AND INACTIVATION OF PROSTAGLANDIN E 2 METHYL ANALOGUES IN THE RAT PULMONARY CIRCULATION
Author(s) -
BAKHLE Y.S.,
JANCAR SONIA,
WHITTLE B.J.R.
Publication year - 1978
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1978.tb08456.x
Subject(s) - circulation (fluid dynamics) , chemistry , prostaglandin , prostaglandin e , medicine , endocrinology , pharmacology , biochemistry , biology , physics , thermodynamics
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 × 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.