Effects of inhibitors of arachidonic acid turnover on the production of prostaglandins by the guinea-pig uterus

Abstract

The supply of free arachidonic acid from phospholipids is generally regarded as the rate-limiting step for prostaglandin (PG) synthesis by tissues. Two enzymes involved in arachidonic acid uptake into, and release from, phospholipids are acyl-CoA:lysophospholipid acyltransferase (ACLAT) and phospholipase A2 (PLA2), respectively. PGF2 alpha produced by the endometrium induces luteolysis in several species including guinea-pigs. Thimerosal, an inhibitor of ACLAT, and aristolochic acid, an inhibitor of PLA2, both reduced, in a concentration-dependent manner, the output of PGF2 alpha from guinea-pig endometrium cultured for 24 h on days 7 and 15 of the oestrous cycle. This study showed that the continual production of PGF 2 alpha by guinea-pig endometrium is not only dependent upon the activity of PLA2 for releasing free arachidonic acid for PGF2 alpha synthesis, but also on the incorporation of arachidonic acid into the phospholipid pool by the activity of ACLAT. The inhibitory effects of thimerosal and aristolochic acid on the outputs of PGE2 and 6-keto-PGF1 alpha were less marked, particularly on day 7 when the low output of PGE2 was unaffected and the output of 6-keto-PGF1 alpha was increased at the lower concentrations of thimerosal. This finding indicates that there are different pools of arachidonic acid bound as phospholipid for the syntheses of PGF2 alpha and 6-keto-PGF1 alpha by guinea-pig endometrium.

Prostaglandin Endoperoxide Synthase 2 (PTGS2) and Prostaglandins F2α and E2 Synthases (PGFS and PGES) Expression and Prostaglandin F2α and E2 Secretion Following Oestrogen and/or Progesterone Stimulation of the Feline Endometrium

“…2009). In addition, the rate‐limiting step in PG production in the cat endometrium may be the availability of AA, as was demonstrated in guinea pig endometrium (Norman and Poyser 2000) and also described in ruminants (Lee and Silvia 1994).…”

Lithium reduces aquaporin-2 transcription independent of prostaglandins

“…However, the lithium-induced increase in COX-2 abundance did not result in elevated prostaglandin levels in media of mpkCCD cells. This absence of increase in prostaglandins may be due to a lack of free arachidonic acid, which is rate-limiting in the production of prostaglandins (7,31,45,49).…”

Expression of acyl‐CoA synthetase 5 in human endometrium and in endometrioid adenocarcinomas

“…There is general agreement that fatty acid metabolism is important for homeostasis in the endometrium as well as for the physiological interaction of the endometrial–ovarian axis 13 . Endometrial expression and the function of several enzymes involved in fatty acid metabolism such as ACSs have been investigated in the past, 2,13 but there is no detailed study about the expression of the isoform ACS5 in human endometrium under normal or pathological conditions. The first evidence for the expression of the ACS isoform ACS5 in the human uterus came from Northern blot hybridization reported by Yamashita 8 .…”

“…Fatty acid metabolism is an important factor in the homeostasis of the endometrium and the physiological interaction of endometrium and ovary 1,2 . In addition to other known mechanisms, dietary fatty acids, e.g.…”

“…Incorporation of arachidonic acid into phospholipids depends on the sequential action of two enzymes, namely acyl‐CoA synthetase (ACS) and acyl‐CoA:lysophospholipid acyltransferase, acting on lysophospholipids 3–5 . Experimental data have demonstrated enzymatic activity of ACS, acyl‐CoA:lysophospholipid acyltransferase, and phospholipase A 2 in the endometrium 2,6 , 7 …”