Arachidonic acid metabolism by the pregnant rat uterus.

  • I. Downing

Student thesis: Doctoral ThesisPhD

Abstract

Prostaglandin biosynthesis by decidual and myometrial micro somes from pregnant rat uteri was investigated by incubation with [1-14C]-arachidonic acid. Arachidonic acid metabolites synthesized by these preparations were separated and identified using TLC procedures. The optimal incubation conditions for maximum biosynthesis were determined. The influence of hydroquinone, GSH, L-cysteine and EDTA, used as cofactors in microsomal incubations, on overall prostaglandin synthesis was examined. The effect of SH group containing cofactors on the ratio of prostaglandins synthesized was also investigated. The effect on prostaglandin biosynthesis by decidual and myometrial microsomes of replacing hydroquinone with other possible 'natural' cofactors was inspected. Of particular interest were biogenic amines such as adrenaline and noradrenaline, which have been postulated as possible endogenous cofactors. The influence of the day of pregnancy on prostaglandin synthesis by decidual and myometrial microsomes was examined with respect to the quantity and type of prostaglandins synthesized. It was found between days 13-22 of pregnancy that prostaglandin biosynthesis increased as pregnancy progressed. Maximum prostaglandin synthesis was observed on day 22 of pregnancy - expected day of delivery. Synthesis declined sharply one day post-partum. The incubation of decidual and myometrial microsomal suspensions with a selection of non-steroidal anti-inflammatory drugs showed that uterine prostaglandin synthetase was inhibited by these drugs and did not differ radically from the inhibition of other prostaglandin synthetases. However, when inhibited by tranylcypromine or metopirone there was no preferential inhibition of one particular prostaglandin as seen by other workers. The most potent drug tested was flurbiprofen. An inhibitor of arachidonic acid metabolism by decidual and myometrial microsomes was found in the microsomal supernatant of decidual, myometrial and placental microsomes. The inhibitor was found to be heat labile, inhibited in a dose dependent manner, and was not due to metabolism of prostaglandins, with the site of action at the cyclo-oxygenase.
Date of Award1979
Original languageEnglish
Awarding Institution
  • University of Bath

Cite this

Arachidonic acid metabolism by the pregnant rat uterus.
Downing, I. (Author). 1979

Student thesis: Doctoral ThesisPhD