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

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.     

Effects of PGE1 on the frog ventricular strip

Résumé Les effets de la PGE₁ ont été étudiés sur les bandelettes ventriculaires isoleés de la grenouille. La PGE₁ augmente la force de contraction de ces préparations. Le propranolol antagonise significantivement les effets de la noradrenaline sans altérer les réponses à la PGE₁. Un bloqueur des récepteurs -adrenergiques, la phénoxybenzamine n'inhibe pas les effets induits par la PGE₁ ou les catécholamines. L'inhibition de la pompe à sodium par l'ouabaine ne modifie pas la réponse du tissu à la PGE₁.

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We should like to thank Prof.D. A. van Dorp (Unilever Research Vlaardingen) for supplying PGE₁.     

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.     

Feeding elicited in sheep by intrahypothalamic injections of PGE1

Résumé Une augmentation de la prise de nourriture a lieu après injection intrahypothalamique du PGE₁ en dose de 21 nmoles, chez les brebis. La température de la cavité abdominale n'est pas affectée par ces injections, sauf une légère augmentation au moment de l'injection et qui peut provenir du maniement des animaux.

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We are grateful to Dr.John E. Pike for the gift of PGE₁.

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This research was supported in part by a Grant-in-aid of the National Science Foundation, Grant No. GB-28836.     

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     

Effect of PGE1 on lipogenesis in perfused rat liver

Summary In perfused livers of 24 hour-fasted rats, PGE₁ (prostaglandin E₁) infused continuously into the perfusate, was found to cause a 45% increase in the incorporation of 1-¹⁴C acetate into liver fatty acids. PGE₁ was found to have no effect, however, on the activity of the key lipogenic enzymes.     

Opposite effect of PGE2 on cAMP levels in human adrenal medulla and pheochromocytoma

Summary PGE₂ (10^–7 M) caused increased cAMP accumulation in 5 pheochromocytomas, while in 3 human adrenal medullae PGE₂ caused a significant decrease of cAMP level on incubating slices in vitro. This finding is discussed in relation to the opposite effect of PGE₂ on catecholamine release from human medulla and pheochromocytoma slices in vitro.Acknowledgment. This paper is part of a Ph. D. thesis of Punya Boonyaviroj.Established Investigator of the Chief Scientist's Bureau, Israeli Ministry of Health.     

Role of 5-hydroxytryptamine in prostaglandin E1-induced potentiation of hexobarbitone hypnosis in albino rats

Summary PGE₁ potentiated, while diclofenac, a prostaglandin synthesis inhibitor, antagonized hexobarbitone hypnosis in rats. PGE₁-induced potentiation of hexobarbitone sleep was inhibited by a 5HT synthesis inhibitor and by a 5HT receptor blocker, suggesting that this potentiation is 5HT mediated.Acknowledgment. The gift of the following drugs are gratefully acknowledged: PGE₁ (Dr.J. E. Pike, Upjohn), diclofenac (Ciba-Geigy), methysergide (Sandoz) and hexobarbitone (Bayer).     

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).     

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.     

Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues

Summary The PGE₂-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino¹]-, [desamino¹] [descarboxy¹⁴] and [d-Lys⁴]-somatostatin similarly to somatostatin, while the [descarboxy¹⁴]-somatostatin exhibits reduced activity; [d-Lys⁹]-somatostatin is ineffective at a higher concentration.The authors acknowledge the technical assistance ofG. Alexander. F. Bellini, D. Mangerel andJ. Rochon and thank Dr.G. Schilling and his associates for the analytical data.     

Inhibitory effect of methionine- and leucine-enkephalin on contractions of the guinea-pig ileum elicited by PGE1

Summary Methionine-enkephalin and leucine-enkephalin (m-enk and l-enk) have been shown to antagonize contractions of the isolated guinea-pig intestine elicited by PGE₁. The inhibitory effect of these 2 pentapeptides is abolished by naloxone.     

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.     

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.     

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.     

Changes in body temperature produced by injecting prostaglandin E1, EGTA and bacterial endotoxins into the PO/AH region and the medulla oblongata of the rat

Résumé La prostaglandine E₁ a causé de l'hyperthermie si on l'injectait dans la région préoptique/hypothalamique antérieure/des rats et de l'hypothermie au niveau de la région médullaire oblongue. L'EGTA, le Piromen et le vaccin typhoïdes ont rarement causé des changements parallèles dans la température rectale si on les injectait dans les deux régions cérébrales.

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This research was supported by PHS Research Grant No. 1-R01-NS-10046-01 from the National Institute of Neurological Diseases and Stroke. We thank Dr.J. Pike of Upjohn Laboratories for supplying the PGE₁.

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Medical student fellow in Psychiatry. Supported by the Hogg Foundation and PHS Grant No. 5 TO2 MH 5928 from the National Institute of Mental Health.     

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.     

Über die Wirkung von Prostaglandin E1 auf den Ca-Haushalt isolierter Meerschweinchenherzen

Summary The stimulatory effect of PGE₁ on different functions of isolated guinea-pig hearts (Langendorff method, Tyrode solution) was coupled with an increase in the rate of⁴⁵Ca uptake from the perfusion medium. The total myocardial Ca content and the amount of exchangeable cellular Ca were not affected. This action of PGE₁ on the myocardial Ca metabolism seems to be related to the positive inotropic action of PGE₁ and can most probably be explained by an increase in the membrane permeability to Ca ions (similar to the action of epinephrine).     

Die Lecithin/Lysolecithin- und Cholesterin/Cholesterinester-Beziehung im Rattenserum bei der Galaktosamin-Hepatose

Summary After single i.p. application of 300 mg/kgd-galactosamine-hydrochloride in male conventional Wistar-II-rats, the concentration of serum cholesterol esters and serum lysolecithin decreases in statistical significance, serum lecithin increases slightly. Because the relation of esterified serum cholesterol to total serum cholesterol increases, it may be that the significant decrease of the cholesterol ester fraction, induced by the slight galactosamine-liver injury, is not only effected by transacylation-inhibition in plasma.

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Unter experimenteller Mitarbeit von cand. med.B. Riese     

A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production

Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE₂ in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay in PGE₂-diminished IL-2 production. The decrease in IL-2 production after PGE₂ and/or luzindole administration correlated with downregulation in the nuclear receptor RORα. We also highlighted a role of cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE₂ in the RORα expression. Finally, a significant RORα downregulation was observed in T cells permanently transfected with inducible MT₁ antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORα expression, opening a new way to understand melatonin regulation in lymphocyte physiology. Received 23 September 2008; received after revision 19 November 2008; accepted 21 November 2008