Analysis of prostaglandins formed from endogenous and exogenous arachidonic acid in homogenates of human reproductive tissues

Dimov, V.; Christensen, Niels Juel; Green, K.

doi:10.1016/0005-2760(83)90079-6

Cited by 26 publications

(2 citation statements)

References 8 publications

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“…Indeed, it was shown that cellular prostanoid synthesis altered dramatically depending on the stimulus used [34,35]. It was also shown that for the types of prostanoids being synthesized by a cell it was very important whether an exogenous or endogenous source of AA was used [36,37]. It was also suggested that PGH synthase‐2 utilized AA liberated from cellular membrane phospholipids by c‐PLA 2 action, whereas in fibroblasts and macrophages PGH synthase‐1 couldn’t use the same process [2,15].…”

Section: Discussionmentioning

confidence: 99%

Kinetics of prostanoid synthesis by macrophages is regulated by arachidonic acid sources

Gonchar

Sergeeva

Mevkh

et al. 1999

European Journal of Biochemistry

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The dependence of prostanoid synthesis on the nature of free arachidonic acid (AA) appearance was investigated in mouse peritoneal macrophages. AA delivery from intracellular sources to the constitutive prostaglandin (PG)H synthase was provided by action of calcium-ionophore A23187; and from extracellular sources by AA addition to the culture medium. It was found that the kinetics of prostanoid synthesis dramatically depends on the sources of AA. Free AA concentration used for prostanoid synthesis is either a constant or a variable value depending upon the sources. The kinetics of cellular prostanoid synthesis can be regulated by the following processes: (a) the irreversible inactivation of PGH-synthase in the course of the reaction (k in ), (b) prostanoid metabolism (k r ), and (c) incorporation of exogenous AA into cellular membranes (k a ). From our experiments and mathematical calculation these parameters were found to be k in = 0.20^0.02 min 21 , k r = 0.17^0.03 min 21 in the case of stimulation with A23187, and k in = 0.0156 min 21 , k r = 0.0134 min 21 , k a = 0.0025 min 21 in the case of exogenous AA addition. The studies of prostanoid biosynthesis by macrophage microsomes led to independent determination of k in = 0.20^0.02 min 21 . This value perfectly fits the kinetics of the prostanoid cell synthesis under endogenous AA supply but shows a 10-fold decrease in the case of exogenous AA supply. Our study on the kinetics of prostanoid synthesis by mouse peritoneal macrophages clearly demonstrate that AA is able to regulate cellular prostanoid synthesis in the presence of constitutive PGH-synthase only. A regulation mechanism based on the co-operation of the constitutive PGH-synthase isoform and the availability of free AA is proposed and could be confirmed by mathematical modelling.Keywords: arachidonic acid; mathematical modelling; prostanoids; peritoneal macrophage; prostaglandin-H synthase Prostanoids, the oxygenated metabolites of arachidonic acid (AA), mediate a wide variety of physiological processes, including ovulation, hemostasis, platelet aggregation, kidney water balance and immune responses [1,2]. Prostanoid production is thought to be regulated by both prostaglandin (PG) H synthases and phospholipases, main of them are considered to be phospholipase A 2 (PLA 2 ) [3±5]. To date, more than 10 forms of PLA 2 have been identified in mammals, among which secretory PLA 2 (s-PLA 2 ) and cytosolic PLA 2 (c-PLA 2 ) have been paid considerable attention [6±9]. Phospholipases release AA from membrane phospholipids then PGH-synthase converts free AA to PGH 2 , the common precursor for all prostanoids. PGH 2 is then enzymaticaly transformed into various prostanoid types, such as PGE 2 , PGF 2a , prostacyclins and thromboxanes.PGH synthase, the rate limiting enzyme in the conversion of free AA to prostanoids, has two distinct activities: a cyclooxygenase activity which catalyses the formation of PGG 2 from arachidonate and a peroxidase activity which reduces the hydroperoxide group of PGG 2 to form PGH 2 ....

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Section: Discussionmentioning

confidence: 99%

Kinetics of prostanoid synthesis by macrophages is regulated by arachidonic acid sources

Gonchar

Sergeeva

Mevkh

et al. 1999

European Journal of Biochemistry

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“…Addition of arachidonic acid to our incubations simulated the increased precursor availability and resulted in a 2-3 fold increase in PGE output, confirming that substrate availability is an important determinant of the rate of PGE synthesis. Okazaki et al (1981) have reported an actual increase in the conversion rate of radiolabelled arachidonic acid into PGE in homogenates of amnion obtained after spontaneous labour compared with tissues obtained at elective caesarean section; but recent studies (Dimov et al 1983) suggest the metabolism of radiolabelled arachidonic acid in tissue homogenates can only be interpreted in a semi-quantitative way.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E production by amniotic cells in relation to term and preterm labour

Bernal

Hansell

Alexander

et al. 1987

BJOG

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Summary. The rate of prostaglandin E (PGE) production was measured in collagenase‐dispersed amniotic cells obtained from 14 women after spontaneous labour at term—seven after spontaneous preterm labour, nine after delivery by elective caesarean section at term and six after induction of labour at term. Cells were incubated with and without arachidonic acid and PGE was estimated by specific radioimmunoassay. Basal PGE output (pmol/106 cells per 3 h) was highest in the spontaneous labour group, 27·5 (SEM 5·5) and lowest in the preterm labour group, 4 (SEM 1·2) (P<0·001). Values in the elective section and induction groups were 13·6 (SEM 2·7) and 10 (SEM 3·1), respectively; these values were significantly higher than in the preterm labour group and the values after induction were significantly lower than after spontaneous labour. Addition of arachidonic acid resulted in a significant increase in PGE output in all groups, but the values after preterm labour remained significantly lower than those of any group at term. These data indicate that towards term there is a maturation in the PG synthetase activity of the amnion and that PGE output in this tissue is increased in spontaneous labour.

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Regulation of T-Cell Activation by Leukotriene B4

Goodwin

1987

Lipid Mediators in the Immunology of Shock

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Analysis of prostaglandins formed from endogenous and exogenous arachidonic acid in homogenates of human reproductive tissues

Cited by 26 publications

References 8 publications

Kinetics of prostanoid synthesis by macrophages is regulated by arachidonic acid sources

Kinetics of prostanoid synthesis by macrophages is regulated by arachidonic acid sources

Prostaglandin E production by amniotic cells in relation to term and preterm labour

Regulation of T-Cell Activation by Leukotriene B4

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