Distribution of arachidonic acid and other fatty acids in the lipids of guinea-pig uterus and plasma in relation to uterine prostaglandin synthesis

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Trifluoperazine, a calmodulin antagonist, inhibited the A23187-induced increase in outputs of prostaglandin (PG) F-2 alpha and 6-oxo-PGF-1 alpha from the Day 7 and Day 15 guinea-pig uterus superfused in vitro. The basal outputs of, and the arachidonic acid-induced increase in outputs of PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha from the guinea-pig uterus were not inhibited by trifluoperazine. In contrast, indomethacin inhibited A23187-stimulated, arachidonic acid-stimulated and the basal outputs of PGs from the guinea-pig uterus, indicating that trifluoperazine was not inhibiting cyclo-oxygenase. Since the action of A23187 is dependent upon extracellular Ca2+, the present findings provide evidence that calmodulin is involved in Ca2+-induced increases in uterine PG output from the guinea-pig uterus. Trifluoperazine, but not indomethacin, inhibited A23187-induced contraction of the guinea-pig uterus, which is consistent with calmodulin being involved in smooth muscle contraction. Arachidonic acid treatment did not contract the guinea-pig uterus. These findings indicate that PGs are not involved in the contraction induced by A23187. Other findings of interest were (i) trifluoperazine caused a small, sometimes significant (P less than 0.05), increase in uterine PG output, (ii) exogenous arachidonic acid failed to increase PGF-2 alpha output from the Day 15 uterus in contrast to the stimulant action of A23187, and (iii) exogenous arachidonic acid caused a fairly large increase in uterine PGE-2 output in contrast to the small effect with A23187.

Section: Discussionmentioning

confidence: 99%

Effect of trifluoperazine, a calmodulin antagonist, on prostaglandin output from the guinea-pig uterus

Poyser¹

1985

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“…Presumably, the calcium ionophore causes an influx of Ca2 + into the uterine cells which in turn stimulates PLA-2 to release arachidonic acid from phospholipids (the major source of arachidonic acid in the guinea-pig uterus; Leaver & Poyser, 1981) for PG synthesis. TMB-8 (150 µ ) completely abolished this stimulatory effect of A23187 on uterine output from the Day-15 guinea-pig uterus indicating that, at this concentration, TMB-8 is able to antagonize fully the effects of a rise in the intracellular free Ca2+ concentration in the uterus.…”

Section: Discussionmentioning

confidence: 99%

Effects of TMB-8, an intracellular calcium antagonist, and W-7, a calmodulin antagonist, on prostaglandin output from the guinea-pig uterus

Poyser¹

1985

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TMB-8, an intracellular Ca2+ antagonist, inhibited the A23187-induced increase in outputs of prostaglandin (PG) F-2 alpha and 6-keto-PGF-1 alpha from the guinea-pig uterus superfused in vitro. The high basal output of PGF-2 alpha from the Day-15 guinea-pig uterus was not inhibited by TMB-8, indicating that a maintained high intracellular free Ca2+ concentration is not necessary for maintaining this high output of PGF-2 alpha. W-7, a calmodulin antagonist, had similar actions except that PGF-2 alpha output from the Day-15 uterus was reduced 20-30 min after the W-7 treatment had stopped. Overall, these findings suggest that, in the guinea-pig, oestradiol acting on a progesterone-primed uterus causes a prolonged stimulation of endometrial phospholipase A-2 in the absence of a maintained high Ca2+ concentration, thus providing a continuous release of arachidonic acid for increased endometrial PGF-2 alpha synthesis during the last third of the oestrous cycle.

“…However, plasma lipids are not the only source of fatty acids for endometrial lipids, as suggested by the relative enrichment in polyunsaturated fatty acids (e.g. arachidonic) in uterine lipids as com¬ pared to blood (Leaver & Poyser, 1981) and by the fact that human endometrium actively incorpo¬ rates [ 1 -' 4C]acetate into polar and neutral glycerolipids (Merrill & Werthessen, 1966). The presence of 22 carbon tetra-, penta-, and hexa-enoic fatty acids suggests that elongating enzymes and desaturases are operative in endometrial tissue since these fatty acids are in exceedingly low concen¬ trations in plasma lipids.…”

Section: Resultsmentioning

confidence: 99%

“…Phosphatidyl-choline and -ethanolamine contribute almost equally to the total arachidonate in endometrium, since although the percentage of arachidonate is twice as low in phosphatidylcholine than in phosphatidylethanolamine, the content of the former is double that of the latter. As in the guinea-pig uterus (Leaver & Poyser, 1981 (Thorburn & Challis, 1979) and prostaglandin synthetase has been detected in various subcellular fractions of endometrium (Wlodawer, Kindahl & Hamberg, 1976). The release of arachidonic and eicosatrienoic acids from endometrial glycerophospholipids is a prerequisite for prostaglandin formation.…”

Section: Resultsmentioning

confidence: 99%

Cyclic changes in phospholipid content and composition in human endometrium during the menstrual cycle

Montané¹,

Pérez-Ballester²

1985

Summary. A significant increase in total phospholipid content of the endometrium took place during the secretory phase of the human menstrual cycle (26% increase from mi d\x=req-\ proliferative to premenstrual stage). The major phospholipid, phosphatidylcholine, was increased by 30%, whereas phosphatidylethanolamine was unchanged. Phosphatidyl-serine and -inositol underwent the largest percentage increases (40%). Phosphatidic acid levels were the only ones to decrease ( \m=-\ 52%), a finding consistent with the role of this lipid as precursor of the increased phospholipids. The changes did not markedly affect phospholipid composition, except for a significant decrease in the proportions of phosphatidate and phosphatidylethanolamine. Arachidonate and eicosatrienoate (n-6) were the major polyunsaturated fatty acids. C22 tetra-, penta-and hexa-enoic fatty acids of the n-3 and n-4 families were also present in all major endometrial glycerophospholipids throughout the cycle. The mass changes in phospholipids during the cycle occurred without alteration of their fatty acid composition.