Arachidonic acid metabolic pathway of the rabbit placenta

Bloch, Michele; McLaughlin, Laura L.; Crowley, Jan R.; Needleman, Philip; Morrison, Adam

doi:10.1016/0090-6980(85)90202-3

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…The placenta converts more effectively (by a factor of 3) than brain tissue the arachidonic acid into lipoxygenase products, presumably because of a higher apparent affinity and greater V, , , value. Evidence for this activity in the rabbit placenta tissue was presented previously by Elliott et al (1984) and Bloch et al (1985). In accord with these reports, we also observe that the lipoxygenase activity resides almost exclusively in the 100,000 g supernatant.…”

Section: Discussionsupporting

confidence: 93%

“…Like the placenta, the fetal brain is also capable of synthesizing 12-HETE and 15-HETE and as expected predominantly by the cellular cytosol (Lindgren et al, 1984). Formation of PGE2, by the placenta as identified by TLC, HPLC, and RIA techniques, is predominantly confined to the particulate fraction, in line with previous studies (Bloch et al, 1985). In contrast, there is little or no PGE2 synthesis by the brain particulate fraction.…”

Section: Discussionsupporting

confidence: 89%

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Arachidonic Acid Oxidation by Brain and Placenta Preparations from Normal and Placental Insufficient Fetal Rabbit

Goldin

Harel

Tomer

et al. 1987

Journal of Neurochemistry

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Cytosolic (100,000 g) fractions of fetal rabbit brain and placenta tissue convert [1-14C]arachidonic acid into several oxidation products identified with the lipoxygenase [12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE] and cyclooxygenase [prostaglandin E2 (PGE2)] pathways. Formation of 12-HETE and 15-HETE by fetal brain is time-dependent, reaching a plateau after 40 min and is linear with protein concentration. An apparent affinity constant of 0.06 mM and a Vmax of 0.1 mumol/h/g wet weight are presumably responsible for the excessive accumulation of 12-HETE and 15-HETE in comparison to PGE2 (Km = 0.5 mM). The latter is synthesized by the placenta particulate fraction but almost exclusively by the brain cytosol. Compared to brain, the activity of the placenta tissue is exceedingly higher and in addition to 12-HETE and 15-HETE there is a substantial formation of 12-L-hydroxyheptadecatrienic acid. Formation of 12-HETE and 15-HETE at 21 days is as effective as at 31 days gestation and is strongly inhibited by nordihydroguaiaretic acid (93%), BW755c (99%), and AA861 (84%) but not by indomethacin. Placenta and brain tissues of intrauterine growth retarded fetuses after ligation of placental blood vessels fail to convert arachidonic acid into other eicosanoids. Loss of enzymatic activity also observed in normal tissue after prolonged storage cannot be restored by the addition of several SH agents, ascorbate, or ferric iron.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Arachidonic Acid Oxidation by Brain and Placenta Preparations from Normal and Placental Insufficient Fetal Rabbit

Goldin

Harel

Tomer

et al. 1987

Journal of Neurochemistry

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“…Considering the questionable activities of P450 and PGS, it appears that arachidonate metabolism in human placenta occurs almost exclusively via the LO pathway. The results of several investigations on the preparations of human [47,80,100,102,104] and rabbit [105] placenta lend a strong support to this postulate. No difference in LT release is observed in the placentas examined after labor at term, after preterm labor, or after Cesarean section [100].…”

Section: Occurrence Of Lomentioning

confidence: 75%

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Kulkarni

2001

CPD

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Many developmental toxicants and teratogens require prior metabolism to reactive species or free radicals to exert toxicity. Thus the knowledge of conceptal biotransformation is absolutely critical in understanding toxicity of these chemicals. Due to extremely low content of cytochrome P450 in the embryo and other conceptal tissues, the research focus in recent years has steadily shifted toward enzymes capable of peroxidative oxidation of xenobiotics. At least three enzymes viz. lipoxygenase, peroxidase and prostaglandin synthase, each capable of peroxidative xenobiotic metabolism, occur in conceptal tissues of man and laboratory animals in biologically significant amounts. This review mainly summarizes the available information on the enzymatic bioactivation of teratogens and developmental toxicants belonging to diverse classes such as drugs, pesticides, environmental contaminants, industrial and other chemicals. Additionally, some discussion is devoted toward issues such as drug-drug interactions. The emerging new information on the peroxidative glutathione conjugate formation from xenobiotics is also presented. A critical need for gathering more information on this subject using different enzyme preparations from human conceptal tissues is stressed to avoid tragedies in the future.

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“…The ability of these tissues to synthesize leuko¬ trienes has been suggested by the detection of hydroxyeicosatetraenoic acid (HETE) production from [14C]arachidonic acid using thin-layer and high-pressure liquid chromatography (HPLC) (Saeed & Mitchell, 1982;Elliott, McLaughlin, Bloch & Needleman, 1984;Bloch, McLaughlin, Crowley et al 1985;Mitchell, 1986;Bennett et al 19876). Further¬ more, leukotrienes may affect uterine contractility (Bennett, Elder & Myatt, 1987a).…”

Section: Introductionmentioning

confidence: 99%

Leukotriene release by human fetal membranes, placenta and decidua in relation to parturition

Rees

Marzo²,

Bernal³

et al. 1988

Journal of Endocrinology

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Complete placentas and membranes were obtained from women after uncomplicated singleton pregnancies. Six were collected after labour at term, six after preterm labour and six after elective Caesarean section at term. Leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) release was examined using a short-term incubation technique. Release by amnion was significantly higher than that by the other tissues for the three modes of delivery. Comparison of LTC4, LTD4 and LTE4 release by individual tissues with regard to the type of delivery showed no significant difference.

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Arachidonic acid metabolic pathway of the rabbit placenta

Cited by 12 publications

References 14 publications

Arachidonic Acid Oxidation by Brain and Placenta Preparations from Normal and Placental Insufficient Fetal Rabbit

Arachidonic Acid Oxidation by Brain and Placenta Preparations from Normal and Placental Insufficient Fetal Rabbit

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Leukotriene release by human fetal membranes, placenta and decidua in relation to parturition

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