Effects of anaesthesia and chronic catheterization on circulating levels of prostaglandins (PGE2 and PGF2a in dogs

Summary Chronic catheterization of aorta and inferior vena cava in dogs did not significantly affect circulating levels of prostaglandins (PGE₂ and PGF_2a ). Pentobarbital (30 mg/kg i.v.) anaesthesia produced a significant decrease in PGF_2a .This work was supported by INSERM (grant No. 76.5.183.5).We wish to thank Miss Laure Eloy and Mrs Annick Soubrier for their technical assistance.     

Alterations in the fraction of oxygen in inspired gas affect rates of renal prostaglandin E2 synthesis in anesthetized dogs

Summary Reductions of oxygen in inspired gas from 20% to 15%, in anesthetized dogs, reduced arterial PO₂ and increased the renal efflux of PGE₂ but not PGF_2a . Renal blood flow, blood pressure, plasma renin activity as well as arterial pH and PCO₂ were unaffected. PGs may mediate the renal hemodynamic or excretory consequences of alterations in PO₂. In addition, minor variations in PO₂ might account, in part, for the variable renal venous PGE₂ concentrations reported under basal conditions.Authentic prostaglandins were supplied by Dr John E. Pike of the Upjohn Company. This work was supported by grants from the Veterans Administration, the Southern Medical Association and U.S. Public Health Service. Dr. Brash is an American Heart Association, Missouri Affiliate Fellow.     

Erythropoietic effects of PGE2 and 2 endoperoxide analogs

Summary The erythropoietic effects in exhypoxic polycythemic mice of two endoperoxide analogs were assessed and compared with PGE₂. The 9a, 11a epoxymethano analog (U-44069) was found to be a much more potent erythropoietic stimulus than the 11a,9a analog (U-46619) or PGE₂.This work was supported by a Senior Research Grant-in-Aid from the American Heart Association-Louisiana (DMG) and USPHS Grant No. AM 13211 (JWF).     

Morphological effects of prostaglandins E1, E2 and F2α on fibroblast-like cultures of human synovial cells

Summary In medium supplemented with serum, PGE₁ and PGE₂ were equally potent in inducing cells with a fenestrated appearance, whereas PGF₂ was comparatively ineffective. In BSA without serum the effects were more persistent and characterized by a high proportion of astrocyte-like cells. The effects were reversed upon removal of the prostaglandins.This work was supported by the National Health and Medical Research Council of Australia.     

A marine mollusc provides the first example of in vivo storage of prostaglandins: Prostaglandin-1,15-lactones

Summary Prostaglandin-(PG) 1,15-lactones and, in smaller amounts, free acids, were isolated from both the mantle and the dorso-lateral appendices of the opisthobranch molluscTethys fimbria. In vivo conversion of PGs into the corresponding lactones and accumulation of PGE₂- and PGE₃-1,15-lactones in the appendages were shown. The detachment of these appendages from the molested mollusc caused the in vivo conversion of PGE₂- and PGE₃-lactones back to PGE₂ and PGE₃ respectively, thus providing the first example of a mechanism by which prostaglandins can be stored and, when needed, released.     

Serum and bile modifications in the guinea-pig following chronic treatment with PGE1 and PGE2

Summary PGE₁ increases cholesterolemia without lipemia modifications. In bile there are not modifications in cholesterol levels and total lipids appear diminished. PGE₂ raise the lipemia and have no effect in cholesterolemia, moreover bile cholesterol and total lipids exhibit no changes. Both PGE₁ and PGE₂ decreased the bile volume.Acknowledgment. The authors wish to express their thanks to the Upjohn Laboratory for kindly furnishing the prostaglandins employed, with the relevant bibliography, and to Mr.F. A. Mori for the English translation.     

The attenuation of prostaglandin-induced luteolysis in decidual tissue-bearing pseudopregnant rats

Summary Decidual tissue (DT)-bearing pseudopregnant (PSP) rats, in contrast to hysterectomized PSP rats, were resistant to a luteolytic regimen of either PGF₂ or PGE₂ when examined for the duration of PSP diestrus. The PG treatments, however, caused a marked fall in the serum progesterone levels on days 10 and 12, although the levels in DT-bearing rats on day 10 were significantly higher than in the hysterectomized rats.Acknowledgment. The authors wish to thank Helen Wilk and Edward Butler for their help in animal care; Ellen O'Laughlin-Phillips for the progesterone assays; Rosa Garnett, Jo Fletcher, and Aileen Svaty for editorial and secretarial help; Dr John E. Pike of the Upjohn Company for the gifts of PGE₂ and PGF₂; and Dr G. N. Niswender for the gift of antiserum GDN-337 used in the RIA for progesterone.Aided in part by NIH Training Grant HD-00024, Ford Foundation Grant 670-0135A, and NIH Program Project HD-07640.     

Prostaglandin E1 induced salivary secretion

Summary PGE₁ but not PGF₂ at 500–1000 g/kg induced a slow and sparse flow from the parotid and no flow at all from submaxillary glands. Composition of PGE₁-induced parotid saliva was quite different from that evoked by any autonomic agonists. The present study suggests that PGE₁ might act directly on parotid acinar cells.Acknowledgment. This work was supported by NIDR grant DE05633. The authors wish to thank Ms Sonya Wynn for her technical assistance.     

Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy

Studies have shown prostaglandin F_2α to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF_2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human FP receptor and found that treatment with PGF_2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF_2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF_2α. This suggests that FP receptor activation of Rho signaling by PGF_2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting properties of PGF_2α. Received 7 July 2005; received after revision 22 October 2005; accepted 11 November 2005     

Effects of PGE2 and PGF2α on the simulation by noradrenaline and oxytocin of human cervical muscle activity at term

Summary Cervical specimens were obtained by needle biopsy in connection with caesarean section at term pregnancy. The preparations were superfused in an organ chamber and contractions were registered isometrically. Prostaglandin (PG) E₂ and F₂ inhibited spontaneous contractions. The stimulatory action of noradrenaline was not influenced by PGF₂ but was reduced by PGE₂ whereas both PGs abolished the excitatory effect of oxytocin.     

Interaction between PGE2 and EGF receptor through MAPKs in mouse embryonic stem cell proliferation

Identifying the small molecules that permit precise regulation of embryonic stem (ES) cell proliferation should further support our understanding of the underlying molecular mechanisms of self renewal. In the present study, we showed that PGE₂ increased [³H]-thymidine incorporation in a time and dose dependent manner. In addition, PGE₂ increased the expression of cell cycle regulatory proteins, the percentage of cells in S phase and the total number of cells. PGE₂ obviously increased E-type prostaglandin (EP) receptor 1 mRNA expression level compare to 2, 3, 4 subtypes. EP1 antagonist also blocked PGE₂-induced cell cycle regulatory protein expression and thymidine incorporation. PGE₂ caused phosphorylation of protine kinase C, Src, epidermal growth factor (EGF) receptor, phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation, and p44/42 mitogen-activated protein kinase (MAPK), which were blocked by each inhibitors. In conclusion, PGE₂-stimulated proliferation is mediated by MAPK via EP1 receptor-dependent PKC and EGF receptor-dependent PI3K/Akt signaling pathways in mouse ES cells. Received 30 January 2009; received after revision 03 March 2009; accepted 10 March 2009     

Etamsylate as inhibitor of prostaglandin biosynthesis in pregnant human myometrium in vitro

Summary The effects of etamsylate on prostaglandin (PG) biosynthesis in microsomes of pregnant human myometrium in vitro have been determined, and compared with those of indomethacin. Both drugs inhibited PG biosynthesis, indomethacin being the more potent inhibitor of the two. Etamsylate inhibited synthesis of 6-oxo-PGF₁, PGF₂, PGE₂, and thromboxane B₂; increasing the concentration of etamsylate increased the inhibition of synthesis. It is suggested that etamsylate has no anti-cyclo-oxygenase activity, but acts by inhibiting the activity of prostacyclin synthetase, endoperoxide reductase, endoperoxide isomerase, and thromboxane synthetase.     

Calcium dobesilate (Doxium) as a prostaglandin synthetase inhibitor in pregnant human myometrium in vitro

Summary This comparative study on the effect of calcium dobesilate and indomethacin on prostaglandin biosynthesis was performed on microsomal fractions of pregnant human myometrium. Both drugs inhibited prostaglandin synthesis, indomethacin being more potent. Calcium dobesilate inhibited, in a dose-dependent manner, the synthesis of 6-oxo-PGF₁, PGF₂, PGE₂ and TXB₂. Its inhibitory action is comparable to that of etamsylate.     

Prostaglandin E2 increases mechanically evoked potentials in the peripheral nerve

Summary Subdermal injections of PGE₂ (5 g) in the rat foot lead to increases in the potentials evoked in sensory nerve branches by the mechanical stimulation of the skin. This sensitization of both A and C fibres complements the previously described hyperalgesic effects of prostaglandins of the E series.     

Effect of prostaglandins and dibutyryl cyclic AMP on the morphology of cells in primary astroglial cultures and on metabolic enzymes of GABA and glutamate metabolism

Summary Prostaglandins (PGE₁) and dibutyryl cyclic AMP (dBc AMP) induce similar morphological changes in astrocytes obtained in primary cultures. PGE₁ and dBc AMP increased 2 enzymes of GABA and glutamate metabolism, GABA-T and AAT, but did not modify GDH and GLN-S. Prostaglandins probably affect the cAMP content of glial cells and act in the same way as dBc AMP on glial cell differentiation.     

Evidence that the prostaglandin-like substances fromPropionibacterium acnes are not identical with PGE2

Summary The prostaglandin-like substances (PLS) isolated fromP. acnes were investigated by reversed phase chromatography and gas chromatography-mass spectrometry. These analyses demonstrated that PLS were not identical with PGE₂, which supports a concept of PLS as a potential mediator of the inflammatory process in acne vulgaris.     

Influence of prostaglandins E1 and E2 on coagulation of rat blood

Zusammenfassung Die Prostaglandine E₁ (PGE₁) und E₂ (PGE₂) haben keinen Einfluss auf die Gerinnung von Rattenblut. Im Gegensatz zu früheren Postulationen können die Ca-Ionen im Plasma nicht von PGE₁ ersetzt werden. PGE₁ beeinflusst die maximale Amplitude des Thrombelastogramms in vitro nach Zugabe von 0.3–6 g/ml, während PGE₂ diesen Effekt nicht aufweist.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

Summary We investigated whether hypothalamic prostaglandin E₂ (PGE₂) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 (IL-1). The present results show that ACTH responses induced by intravenous injection of IL-1 were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE₂ stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE₂. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE₂.     

Induction of neovascularization in vivo by glycerol

Glycerol, injected into a site between the femoral vessels of the rat, induced neovascularization, both from the preexisting microcirculation and from the side of the femoral vein facing the artery-vein interstitium where the glycerol was administered. The use of glycerol together with a known angiogenic substance (PGE₂) did not modify the neocapillary density (NCD) obtained with glycerol alone. In contrast, the lower level of NCD achieved with an acylglycerol (triacetylglycerol) was increased when the latter was associated with PGE₂. Values reached were similar to, but never higher than, those for glycerol alone, or combined with PGE₂. The results suggest that glycerol and some substances containing glycerol, amongst which 1-butyrylglycerol has been previously considered¹, may stimulate angiogenesis by a direct or indirect mechanism of action.     

Effects of prostaglandins PGE1 and PGF2α on oxygen consumption,sodium and potassium content of renal tissue

Résumé Chez le rat la prostaglandine E₁ augmente la consommation d'oxygène et la teneur en potassium, tandis qu'elle abaisse la teneur en sodium dans le tissu rénal et hépatique. On y a observé une corrélation entre l'effet et la dose de PGE₁ employée. Cependant dans les coupes du tissu hépathique, la PGE₁ est restée sans action. A même dose la PGF₂ a produit des effets comparables à ceux qu'on obtient avec la PGE₁. Ces résultats indiqueraient que la réponse natriurétique à la PGE₁ ne semble pas due à une inhibition de la pompe de sodium des cellules tubulaires, mais à une élévation du flux sanguin rénal.

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The authors wish to express their sincere thanks to Dr.M. Cereijido for his valuable criticism of this work and to MissL. A. Vargas andMr. G. Jordan for their competent technical assistance.

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This work was supported by a grant from the CONICET and CondesaAna Thyssen de Zichy.