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The control of arachidonic acid turnover in relation to prostaglandin production by the guinea-pig uterus

ACS, ACLS and PLA<SUB>2</SUB> activities were detected in guinea-pig endometrium on both 7 (day of low PGF<SUB>2α</SUB> output) and day 15 (day of high PGF<SUB>2α</SUB> output) of the oestrous cycle and in the endometrium of ovariectomizd guinea-pigs treated with oestradiol and/or progesterone. Treatment with aristolochic acid (ARA) and quinacrine (QUIN) (PLA<SUB>2</SUB> inhibitors) significantly (P ¸0.05) reduced PG<SUB>2α</SUB> output from both day 7 and day 15 endometrium cultured for 24 h, demonstrating the crucial role that PLA<SUB>2</SUB> plays in the regulation of AA release for PGF<SUB>2α</SUB> synthesis in the guinea-pig. Unexpectedly, treatment with p-hydroxymercuribenzoic acid (HMB0 and thimerosal (THM) (ACS and ACLS inhibitors) also significantly (P < 0.05) decreased PGF<SUB>2α</SUB> output. However, during long term inhibition of ACS and ACLS, since the rate of uptake of AA into lysophospholipids will be reduced, the amount of AA appropriately placed in the <I>sn</I>-2 position of appropriate phospholipids for the action of PLA<SUB>2</SUB> will also be reduced. Therefore, PLA<SUB>2</SUB> may be indirectly inhibited by a lack of substrate. ACS, ACLS and PLA<SUB>2</SUB> activities were detected in the endometrium and conceptus of early pregnant (day 15) guinea-pigs. All three enzymes were also detected in the endometrium, chorio-allantoic placenta, chorion and amnion of day 29 and 36 pregnant guinea-pigs. Treatment with THM and ARA of day 22, 29 and 36 pregnant guinea-pig endometrial and fetal tissues during 24 h culture suggested that the control of AA uptake is important in the maternal placenta, fetal placenta, chorion and amnion, and that PLA<SUB>2</SUB> appears to have an essential role in the control of PG synthesis from the endometrium, chorion and amnion of pregnant guinea-pigs. ACS, ACLS and PLA<SUB>2</SUB> may have a role in the control of arachidonic acid turnover, and therefore PG production, in guinea-pig uterine and fetal tissues. The stimulus responsible for increased PLA<SUB>2</SUB> activity towards the end of the cycle, and the mechanism of the anti-luteolytic factor provided by the guinea-pig conceptus, remains obscure. The control of AA uptake in the placenta and fetal membranes seems to have a role in the delicate regulation of PG synthesis during pregnancy.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660045
Date January 1998
CreatorsNorman, Sophie Johanna
PublisherUniversity of Edinburgh
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://hdl.handle.net/1842/26816

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