Regional and species differences in endogenous prostaglandin biosynthesis by brain homogenates

Abdel-Halim, M.Saeed; Änggård, Erik

doi:10.1016/s0090-6980(79)80009-x

Cited by 103 publications

(11 citation statements)

References 4 publications

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“…In the central nervous system of rats, PGD2 is identified as the major PG among various PGs and thromboxanes (18)(19)(20). The biosynthesis and degradation of PGD2 in the brain have been well studied (20,21).…”

Section: Discussionmentioning

confidence: 99%

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Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide.

Ueno¹,

Narumiya²,

Ogorochi³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

139

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The intraperitoneal administration of lipopolysaccharide from SalmoneUa typhimurium (1 mg/kg) caused a fall in the rat colonic temperature of about 2TC at an ambient temperature of 22 ± 3TC. The hypothermia induced by the lipopolysaccharide was abated in a dose-dependent manner by the administration of indomethacin. Other inhibitors of prostaglandin synthetase such as aspirin, flufenamic acid, and phenylbutazone had effects similar to those of indomethacin. When various prostaglandins were injected intracerebroventricularly, only prostaglandin D2 caused a dose-dependent fall in the colonic temperature at doses between 1.2 and 6 nmol/kg. Microinjection of prostaglandin D2 into the preoptic area caused hypothermia of about 1°C. However, injection ofprostaglandin D2 into the posterior hypothalamus had little effect on the colonic temperature. The hypothermia caused by prostaglandin D2 was not abated by the administration of indomethacin. The amount of prostaglandin D2 increased significantly in the preoptic/hypothalamic region of rat brain 1 hr after the intraperitoneal administration of the lipopolysaccharide, whereas such increase was not observed in rats pretreatedwith indomethacin. The in vitro incubation ofthe preoptic/ hypothalamic slices with the lipopolysaccharide also increased the amount of prostaglandin D2. These results suggest that the intraperitoneal administration of the lipopolysaccharide induces the release of prostaglandin D2 in the preoptic/hypothalamic area of rat brain and that the latter compound is involved in the hypothermic response of rats to the lipopolysaccharide.Since Milton and Wendlandt found that prostaglandin (PG) E1 is a potent pyrogenic agent in cats in 1970 (1) and Vane's discovery that antiinflammatory and antipyretic drugs inhibit PG synthesis (2), the rise in body temperature caused by pyrogens has been considered to be mediated by the formation of PG(s) in the brain (3-8). The E series PGs have been identified in the brain as well as in the cerebrospinal fluid and suggested as a mediator of hyperthermia by Milton and co-workers (5-8), although Cranston et al. reported results contradicting this hypothesis (9-11). Bacterial endotoxin [lipopolysaccharide (LPS)] is a pyrogen that causes fever in a variety ofmammals. However, in rodents, such as rats, guinea pigs, and mice, it causes hypothermia instead of hyperthermia (12)(13)(14)(15)(16)(17). Recently the PG profile in the brain ofthese animals was clarified and PGD2 was found to be the major PG (18)(19)(20). The synthesis and degradation of PGD2 in the brain have been studied extensively in our laboratory (20,21). In this communication, we demonstrate that indomethacin and other inhibitors of PG synthesis abate the hypothermia of rats induced by the intraperitoneal administration of LPS from Salmonella typhimurium and that PGD2 in the brain is at least in part responsible for the hypothermia.MATERIALS AND METHODS Intraventricular Injection of PGs. Male Wistar rats weighing 380-420 g were anesthetized with intraperiton...

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Section: Discussionmentioning

confidence: 99%

“…However, in rodents, such as rats, guinea pigs, and mice, it causes hypothermia instead of hyperthermia (12)(13)(14)(15)(16)(17). Recently the PG profile in the brain ofthese animals was clarified and PGD2 was found to be the major PG (18)(19)(20). The synthesis and degradation of PGD2 in the brain have been studied extensively in our laboratory (20,21).…”

mentioning

confidence: 99%

Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide.

Ueno¹,

Narumiya²,

Ogorochi³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

139

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“…PGD2 was not measured, even though it is the most abundant prostanoid in rat brain (Abdel-Halim and Anggard, 1979), owing to its facile transformation to dehydration products (Fitzpatrick and Wynalda, 1983). PGE,, on the other hand, was of special interest considering its postulated involvement in diverse central processes (Coceani, 1987).…”

Section: Radioimmunoassaymentioning

confidence: 99%

“…The limit of detection of PGE2 and TXB 2 was, respectively, 0.5-2.5 pg (0.08-0.25 pmol/mg protein) and 2.5 pg (0.09-0.33 pmol/mg protein). Both compounds showed insignificant crossreactivity among themselves and against other prostanoids (i.e., PGD2, PGF2c, 6-keto-PGF1^,) and LT (i.e., LTB 4 and peptidoLT) pressent in the rat brain (Abdel-Halim and Anggard, 1979;Miyamoto et al, 1987). LTC4 and LTE4 were also measured directly in samples with antibodies provided by Dr. B. Peskar, University of Bochum.…”

Section: Radioimmunoassaymentioning

confidence: 99%

Eicosanoid formation in the rat cerebral cortex

Bishai

Coceani

1992

Molecular and Chemical Neuropathology

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Despite the extensive literature on brain eicosanoids, no information is available on the cellular source of individual compounds in the mature organ and the relative contribution of different cell types to the total synthetic product. To address this problem, neurons and glia were isolated from the cerebral cortex of the adult rat by a process comprising, in order, trypsinization, selective sieving, differential centrifugation, and density gradient centrifugation. Enrichment of cells in the appropriate fractions was verified by morphological, immunocytochemical, and biochemical criteria. Both neuron- and glia-rich fractions retained synthetic activity throughout the period of incubation (max. 60 min). Among the eicosanoids examined, prostaglandin (PG) E2 was the predominant compound, followed by leukotriene (LT) E4 and thromboxane (TX) B2, whereas LTC4 occurred in minimal amounts. Although the rank order of eicosanoids did not vary with the cell type, absolute values of PGE2 and TXB2 were greater with neurons. PGE2 synthesis was increased by supplementation of the medium with arachidonic acid (2.6 microM), whereas indomethacin (5.6 microM) had the opposite effect. Conversely, LT synthesis was not altered by arachidonic acid and was only marginally reduced by the 5-lipoxygenase inhibitor, U-60,257 (10 microM). Several agonists (12-O-tetradecanoyl-phorbol-13-acetate, TPA; Ca ionophore A23187; platelet-activating factor; endotoxin; recombinant IL-1) were tested on both neuron- and glia-rich fractions but none of them had an effect. We conclude that freshly isolated neurons and glia are viable insofar as the basal rate of eicosanoid synthesis is concerned. No qualitative difference was noted between the two cell types in the spectrum of products formed and the spectrum itself accorded with early data on the biosynthetic activity of the intact tissue in vivo. Our isolation procedure appears useful for the analysis of the cellular source of eicosanoids under resting conditions, although it cannot be applied to the study of the site and mode of action of activators.

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“…PGD2 was also reported to be an inhibitor of platelet aggregation (19). Although Abdel-Halim et al (20,21) slices, the physiological function of PGD2 in the central nervous system remains obscure. Our data show that PGD2 is a specific and potent activator of adenylate cyclase of cultured neuroblastoma cells.…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin D2, a neuromodulator.

Shimizu¹,

Mizuno²,

Amano³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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The distribution of prostaglandin D synthetase activity was determined in various tissues of rat by using the supernatant fraction (10,000 X g, 20 min) of the homogenates. The highest activity was found in brain, spinal cord, and alimentary tract. The activity was ubiquitously distributed in all parts of brain, and the highest specific activity was found in hypothalamus and thalamus. Homogenates of two neuroblastoma cell lines were found to produce prostaglandin D2, whereas a glioma cell line was almost inactive. Prostaglandin D2 is a potent and specific activator of the adenylate cyclase system of cultured neuroblastoma cells, suggesting the possibility that it may act as a neuromodulator in the central nervous system.Prostaglandin (PG) D synthetase (isomerase) was first detected in the cytosol fraction of various rat tissues (1). Recently, the enzyme was purified to homogeneity from rat brain (2) and clearly distinguished from glutathione S-transferase. To clarify the physiological role of PGD2, we carried out a systematic survey of the enzyme's distribution. In this report, we present quantitative data on the occurrence of PGD synthetase in rat tissues, particularly in brain and cultured neuroblastoma cells. Furthermore, PGD2 at about 10 nM was demonstrated to increase the cyclic AMP level rapidly in the neuroblastoma cells. The possible significance of these findings is discussed. MATERIALS AND METHODSMaterials. [1-14C]Arachidonic acid (60.2 mCi/mmol;/Ci = 3.7 X 1010 becquerels) was purchased from the Radiochemical Centre (Amersham). Arachidonic acid was a product of P-L Biochemicals. PGD2, -E2, -E1, -F2,,, -F20, and -B2, 6-keto-PGFi,, and thromboxane B2 were kindly donated by M.Hayashi (Ono Central Research Institute). L-Norepinephrine bitartrate, 3-hydroxytyramine (dopamine) HCl, DL-propranolol-HCI, 9,10-dihydroxyergotamine tartrate, and 3-isobutyl-1-methylxanthine (IBMX) were obtained from Sigma. Naloxone.HCI and chlorpromazine.HCI were generous gifts from Endo Laboratories and Takeda Research Laboratories (Osaka), respectively. Dithiothreitol and p-chloromercuribenzoic acid were supplied by Wako Pure Chemicals (Osaka); 1-chloro-2,4-dinitrobenzene and phenoxybenzamine.HCI were from Tokyo Kasei Kogyo (Tokyo); and precoated silica gel F254 glass plates were from E. Merck (Darmstadt). [1-'4C]PGH2 was prepared as described (2).Preparation of Tissue Homogenates. Male Wistar rats (300-350 g) were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg/kg), perfused with 200 ml of ice-cold saline, and killed by exsanguination. Eleven organs (whole brain, spinal cord, lung, heart, liver, stomach, small intestine, kidney, spleen, adrenal gland, and vesicular gland)The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 6231were quickly removed. The brain was chilled on ice and separated into 11 parts-cerebral neocortex, cerebellum, pon...

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Regional and species differences in endogenous prostaglandin biosynthesis by brain homogenates

Cited by 103 publications

References 4 publications

Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide.

Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide.

Eicosanoid formation in the rat cerebral cortex

Prostaglandin D2, a neuromodulator.

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