Prostaglandin Profiles in Tissue and Blood Vessels from Human Brain

Abdel-Halim, M.Saeed; Holst, Hans von; Meyerson, Björn A.; Sachs, Charlotte; Änggård, Erik

doi:10.1111/j.1471-4159.1980.tb09980.x

Cited by 111 publications

(25 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These RIA results may be somewhat complicated by the observed non-enzymatic isomerization of PGH 2 to PGE 2 as indicated in table 1. Thus, PGE^ release may not reflect enzymatic production of the prostanoid, but rather the sum of enzymatic and spontaneous isomerization of PGH 2 The results from this study do not support the general theory that hypoxia is a stimulus to enhance prostaglandin release. The results from this study suggest that the rate of release of 6-keto PGF |Q may be related to O 2 tension, as would be predicted by the O 2 requirement of the cyclooxygenase enzyme.…”

contrasting

confidence: 82%

“…The concentration of immunoreactive 6-keto PGF la (the stable hydrolytic product of PGI 2 ) and immunoreactive PGE 2 were determined in nonextracted samples of PBS that had been incubated with isolated rabbit cerebral microvessels. Antisera was kindly supplied by Dr. Lawrence Levine (Brandeis University, Waltham, MA).…”

Section: Radtoimmunoassay Of Pge 2 and 6-keto Pgf Amentioning

confidence: 99%

“…Homogenates (equivalent to 100 fig protein) prepared from rabbit cerebral microvessels were incubated with [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C] PGH 2 (25,000 dpm, 0.2 nmol) in the presence and absence of reduced glutathione (GSH). Control incubations used boiled homogenates or rabbit serum albumin.…”

Section: Metabolism Of [1-i4 C] Pgh 2 By Rabbit Cerebral Mkxovessel Hmentioning

confidence: 99%

See 2 more Smart Citations

Prostaglandin release from isolated rabbit cerebral cortex micro-vessels--comparison of 6-keto PGF1 alpha and PGE2 release from micro-vessels incubated in 100% O2, room air and 95% N2:5% CO2.

Rodrigues¹,

Gerritsen²

1984

Stroke

View full text Add to dashboard Cite

SUMMARY Prostaglandin release from microvessels isolated from the rabbit cerebral cortex was determined under three different atmospheric conditions: 100% O 2 ("O 2 ") room air, and 95% N 2 =5% CO 2 ("N 2 -COj"). Initial studies with homogenates prepared from rabbit cerebral microvessels (RCMV) indicated two pathways of enzymatic PGH 2 transformation, namely PGI 2 synthase and GSH-dependent PGH-PGE isomerase. We measured the release of the principal products of these pathways, 6-keto PGF |a and PGE, from freshly prepared RCMV. The release of 6-keto PGF |a exceeded that of PGE^ in all three protocols. RCMV incubated in "N 2 -CO 2 " exhibited a reduction in the release of 6-keto PGF la compared to room air or "O 2 " incubated RCMV, evident at 30-60 min of incubation. No significant differences in the release of PGE 2 were observed among the three incubation protocols. In all three incubation protocols the ratio of 6-keto PGF |a to PGE 2 did not differ during the initial 10 minutes of each incubation. After 30 to 60 min of incubation, this ratio did not change from the "O 2 " or room air treated RCMV, but decreased significantly for the "N 2 -CO 2 " treated group. To determine the reversibility of the apparent "N 2 -CO 2 " induced decline in 6-keto PGF |a release, microvessels were removed from the nitrogen atmosphere and incubated in room air. Release was measured during the initial 10 min following reintroduction to room air and was compared to room air pretreated controls treated in an identical manner. Complete recovery of 6-keto PGF |a production was observed, and an enhanced ratio of 6-keto PGF lo to PGE 2 observed in the "N 2 -CO 2 " treated RCMV. In view of the opposing actions of PGI 2 (vasodilator) and PGE 2 (mild vasoconstrictor) on cerebrovascular tone, this study suggests that release of prostaglandins by the microvasculature may participate in the cerebrovascular response to ischemia. In addition, this study suggests that the release of 6-keto PGF |n and PGE 2 by cerebral microvessels may be regulated independently.Stroke Kenzie 9 have shown that injection of indomethacin in baboon induces a decrease in CBF, proposed by these authors to be due to inhibition of prostacyclin synthesis by vascular endothelium. Pickard and Mackenzie 9 also demonstrated a reduction in the CBF response under hypercapnic conditions when indomethacin is administered. However, a recent study by Wennmalm and co-workers 10 indicates the effects of indomethacin on basal and hypercapnic CBF (in man) is not due to the effects of indomethacin on PGI 2 (or other prostaglandins) synthesis and release in the cerebral circulation. In this study, these authors compared the effects of indomethacin, naproxen and aspirin on CBF under basal and hypercapnic conditions. Administration of all three drugs eliminated arachidonic acid induced platelet aggregation in platelets obtained from the treated patients. Only indomethacin, and only when given acutely, elicited a decrease in CBF under basal or hypercapnic conditions. Additionally, these auth...

show abstract

contrasting

confidence: 82%

Section: Radtoimmunoassay Of Pge 2 and 6-keto Pgf Amentioning

confidence: 99%

Section: Metabolism Of [1-i4 C] Pgh 2 By Rabbit Cerebral Mkxovessel Hmentioning

confidence: 99%

See 1 more Smart Citation

Prostaglandin release from isolated rabbit cerebral cortex micro-vessels--comparison of 6-keto PGF1 alpha and PGE2 release from micro-vessels incubated in 100% O2, room air and 95% N2:5% CO2.

Rodrigues¹,

Gerritsen²

1984

Stroke

View full text Add to dashboard Cite

show abstract

“…13 Prostaglandin synthesis in cerebral vessels appears to be oriented toward prostacyclin production, while that in nonvascular intracranial tissue tends to be oriented toward the synthesis of other eicosanoids, Chyatte Prevention of Vasospasm depending on species. 12 ' 19 Following synthesis, stable prostaglandins are rapidly cleared from the cerebral extracellular space by facilitated transport rather than by metabolic degradation. Transport from the brain to the blood stream occurs so rapidly that lumbar CSF levels bear little relation to bulk cisternal levels.…”

Section: Discussionmentioning

confidence: 99%

Prevention of chronic cerebral vasospasm in dogs with ibuprofen and high-dose methylprednisolone.

Chyatte

1989

Stroke

View full text Add to dashboard Cite

Severe chronic cerebral vasospasm was produced in dog basilar arteries by two injections, 2 days apart, of autologous blood into the cisterna magna of 25 dogs. Treatment with ibuprofen (ra=8) or high-dose methylprednisolone (n=8) after the first injection of blood prevented or reduced angiographic vasospasm. Cerebrospinal fluid concentrations of prostaglandin E 2 , prostaglandin F 2a , 6-ketoprostaglandin F l a (a metabolite of prostacyclin), and thromboxane B 2 (a metabolite of thromboxane A 2 ) were measured in both treated and untreated (n=7) dogs. In untreated dogs, the level of prostaglandin E 2 increased 94-fold by Day 8 after the first injection of blood and was strongly and positively correlated with the degree of angiographic vasospasm. Treatment with ibuprofen and high-dose methylprednisolone prevented or significantly reduced this increase in prostaglandin E 2 concentration. Smaller increases in cerebrospinal fluid concentrations of thromboxane B 2 and 6-ketoprostaglandin ¥ la occurred after experimental subarachnoid hemorrhage; the magnitude of these increases was also reduced by ibuprofen or high-dose methylprednisolone treatment. In contrast, prostaglandin F 2a levels were not significantly altered during the study. These data show that enhanced prostaglandin E 2 synthesis occurs during experimental subarachnoid hemorrhage, and the by-products generated in its synthesis may play a role in the pathogenesis of cerebral vasospasm.

show abstract

“…Previously, PGD2 had not been thought to be produced in human brain (8,9). However, a considerable amount of PGD2 was detected in postmortem human brains by both radioimmunoassay and gas chromatography/ mass spectrometry (10).…”

mentioning

confidence: 99%

Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins.

Nagata

Suzuki

Igarashi

et al. 1991

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

168

121

View full text Add to dashboard Cite

ABSTRACTcDNAs for glutathione-independent prostaglandin D synthase were isolated from cDNA libraries of human brain. The longest cDNA insert was 837 base pairs long and contained a coding region of 570 base pairs corresponding to 190 amino acid residues with a calculated Mr of 21,016. Between two cDNA inserts isolated from the two different libraries, nucleotide substitutions were observed at 16 positions, including conservative amino acid substitutions at 2 positions and nonconservative substitutions at 5 positions, indicating genetic heterogeneity of this enzyme in humans. The computer-assisted homology search revealed that the enzyme is a member of the lipocalin superfamily, comprising secretory hydrophobic molecule transporters, showing the greatest homology (28.8-29.4% identity; 51.3-53.1% similarity) to a1-microglobulin among the members of this superfamily. In a phylogenetic tree of the superfamily, this enzyme, a,-microglobulin, and the y chain of the complement component C8 form a cluster separate from the other 14 members. The two distinctive characteristics of glutathione-independent prostaglandin D synthase, as compared to the other members ofthis superfamily, are its enzymatic properties and its association with membranes that were probably acquired after evolutionary divergence of the two lipocalins. Based on the observed sequence homology, the tertiary structure of the enzyme was deduced to consist of an eight-stranded anti-parallel ,B-barrel forming a hydrophobic pocket. Furthermore, the Cys-65 residue in the pocket, which is conserved only in the human and rat enzymes but not in other lipocalins, was considered to be a putative active site of the enzyme.Prostaglandin (PG) D2 is a major PG in rat brain and shows several central actions in vivo such as sleep induction, regulation of body temperature, anticonvulsion, suppression of luteinizing hormone release, nociception, and modulation of odor responses. In vitro it also regulates the growth and differentiation of rat glioma C6BU-1 cells and induces Ca2+ influx and cGMP formation in mouse neuroblastoma-rat glioma hybrid NG108-15 cells (for reviews, see refs. 1 and 2). In brief, PGD2 functions as a neuromodulator and/or trophic factor in the central nervous system. Glutathione (GSH)-independent PGD synthase [prostaglandin-H2 D-isomerase; (5Z,13E)-(15S)-9a,11a-epidioxy-15-hydroxyprosta-5,13-dienoate D-isomerase, EC 5.3.99.2] catalyzes the conversion of PGH2 to PGD2 in the presence of various sulfhydryl compounds (3). This enzyme is responsible for biosynthesis of PGD2 in the brain, while several other enzymes, such as GSH-requiring PGD synthase and GSH S-transferase, also catalyze the reaction to produce PGD2 and are present in various other rat tissues (4). The enzyme is localized in the central nervous system (4) and associated tissues, such as the retina (5) and cochlea (6). Furthermore, postnatal changes in the cellular localization of this enzyme have been observed in the brain (7) and cochlea (6). For example, the enzyme is distributed in m...

show abstract

Prostaglandin Profiles in Tissue and Blood Vessels from Human Brain

Cited by 111 publications

References 9 publications

Prostaglandin release from isolated rabbit cerebral cortex micro-vessels--comparison of 6-keto PGF1 alpha and PGE2 release from micro-vessels incubated in 100% O2, room air and 95% N2:5% CO2.

Prostaglandin release from isolated rabbit cerebral cortex micro-vessels--comparison of 6-keto PGF1 alpha and PGE2 release from micro-vessels incubated in 100% O2, room air and 95% N2:5% CO2.

Prevention of chronic cerebral vasospasm in dogs with ibuprofen and high-dose methylprednisolone.

Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins.

Contact Info

Product

Resources

About