Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary removal of [3H]prostaglandin E1 ([3H]PGE1) was measured by double indicator-dilution techniques after bolus injections of indocyanine green and trace amounts of [3H]PGE1 before and after 1-3 h of total cardiopulmonary bypass (CPB) or 3 h of left-heart bypass (LHB) in 18 anesthetized dogs. Before bypass, pulmonary removal was 85.7 +/- 1.2% (means +/- SE, n = 18) and was unchanged on restoration of normal circulation after 1-2 h of CPB (80.6 +/- 1.8%, n = 7) or 3 h of LHB (87.4 +/- 1.6%, n = 4). However, on restoration of normal pulmonary arterial blood flow after 3 h of CPB, removal was significantly decreased to 74.5 +/- 2.2% (P less than 0.01, n = 7). Postbypass depression of [3H]PGE1 removal may explain our previous observations that intrabypass elevations in endogenous immunoreactive prostaglandin E in dogs were not entirely reversible on cessation of 3-4 h of CPB. Possible factors underlying depression of post-CPB pulmonary removal of [3H]PGE1 include: 1) local saturation of [3H]PGE1 removal secondary to intrapulmonary or intravascular release of prostaglandin E, 2) inhibition of prostaglandin dehydrogenase activity, or 3) damage to endothelial cell transport of [3H]PGE1 from the pulmonary microcirculation.
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PMID:Depressed pulmonary removal of [3H]prostaglandin E1 after prolonged cardiopulmonary bypass. 720 Sep 70

Exposure to hypoxia (10% O2 for 5 to 7 days) results in increased survival and decreased pulmonary toxicity of adult rats subsequently exposed to hyperoxia (> 97% O2). These experiments tested whether hypoxia preexposure minimized the decrease in lung metabolism of prostaglandin E1 (PGE1), a vasoactive and antiinflammatory prostaglandin, caused by hyperoxia. Transpulmonary PGE1 clearance was measured as fractional metabolism of PGE1 (2 microM to 30 microM) infused during a 45-second period in an isolated, buffer-perfused rat lung preparation after exposure of rats to one of the following conditions: (1) hyperoxia (> 97% O2 for 48 hours), (2) hypoxia (10% O2 for 120 hours), or (3) hypoxia followed by hyperoxia. Hyperoxia exposure decreased both lung PGE1 metabolism and lung prostaglandin dehydrogenase activity (PGDH). Hypoxia also decreased lung PGE1 metabolism but, in contrast, increased lung PGDH activity. Hypoxia preexposure did not prevent the depression of PGE1 metabolism or PGDH activity caused by hyperoxia, which indicates that survival in hyperoxia did not depend on lung PGE1 metabolism. Hypoxia itself impaired transpulmonary metabolism of PGE1 despite increasing PGDH activity, which suggests possible interference with substrate delivery.
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PMID:Effects of hypoxia and hyperoxia on lung prostaglandin E1 metabolism. 907 31

We have previously shown in the sheep fetus at 0.7 and 0.9 gestation that the choroid plexus, unlike brain parenchyma, catabolizes prostaglandins (PGs). Peculiarly, in the choroid plexus, PGE(2) catabolism persists throughout the neonatal period to abate in the adult, while PGF(2alpha) catabolism abates shortly after birth. To explain this differential behavior and elucidate the function of catabolic enzymes, we examined the cellular location and activity of the rate-limiting enzyme for PGE(2) and PGF(2alpha) catabolism, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Immunofluorescence histochemistry and immunogold electronmicroscopy revealed abundant 15-PGDH expression in the epithelial cytosol close to the brush-border membrane at 0.7 and 0.9 gestation. In contrast, at 5 and 15 days postnatal, 15-PGDH was found throughout the cytosol of stromal fibroblasts. No staining was observed at either location in pregnant adults. PGF(2alpha) catabolism was minimal in the total homogenate and 100000xg supernatant of the fetal choroid plexus at 0.7 and 0.9 gestation, while PGE(2) catabolism was evident at 0.7 gestation only. In contrast, both PGs were catabolized in minced specimens at either age. In conclusion, our study shows immunoreactive 15-PGDH in the choroid plexus from fetal and neonatal, but not pregnant adult, sheep. Results suggest that PGE(2) catabolism is not as critically dependent as that of PGF(2alpha) on tissue integrity and 15-PGDH location. Given the key role being assigned to the choroid plexus in PG removal from brain, we speculate that persistence of PGE(2) catabolism into the early postnatal period protects against central respiratory depression caused by the compound during this susceptible stage of development.
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PMID:Perinatal changes in choroidal 15-hydroxyprostaglandin dehydrogenase: implications for prostaglandin removal from brain. 1087 27

Prostaglandin E2 (PGE2) is an important inflammatory mediator and considered to be involved in the pathophysiology of depression. Previous studies that investigated the role of PGE2 in depression solely concentrated on the cyclooxygenase-dependent synthesis of this bioactive lipid. However, enzymes that degrade PGE2, such as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), have not yet been explored. The present study examined the expression of 15-PGDH in an animal model of depression. Depressive-like behaviors were measured after rats were exposed to chronic unpredictable mild stress (CUMS). 15 PGDH mRNA and protein expression and activity and PGE2 levels were detected in the brain and lungs in stressed animals. The stressed animals exhibited decreases in body weight gain, locomotor activity in the open field, and sucrose preference. The hypothalamus and lungs had high baseline 15-PGDH mRNA and protein expression, whereas the frontal cortex and hippocampus showed no detectable 15-PGDH mRNA or protein expression. 15 PGDH mRNA and protein expression was significantly downregulated in the hypothalamus and lungs in stressed rats compared with control rats, and the enzymatic activity of 15-PGDH was correlated with protein expression levels. PGE2 concentrations in the brain and serum increased in stressed rats. These results suggest the loss of 15-PGDH expression in depression, and 15-PGDH may be a novel potential pharmacological target for the treatment of depression.
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PMID:Chronic unpredictable mild stress induces parallel reductions of 15-PGDH in the hypothalamus and lungs in rats. 2577 23