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

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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     

Geometrical constructions equivalent to non-linear algebraic transformations of the plane in Newton's early papers

Summary The theory of constructive formation of plane algebraic curves in Newton's writings is discussed in § 1: the apparatus by which Newton forms the curves, Newton's theorems on forming unicursal curves, his theory of conics, and his theory of (m, n) correspondence. Special Cremona plane and space transformations obtained by Newton's organic method are dealt with in § 2. The article ends with § 3, which shows two different directions in the theory of the constructive formation of plane algebraic curves in the XVIII-XIXth centuries. A synopsis is appended.Abbreviations MPN The Mathematical Papers of Isaac Newton, edited by D. T. Whiteside, Vols. 1–3, Cambridge, 1967–1969 - Hudson H. Hudson, Cremona Transformations in Plane and Space, Cambridge, 1927 - PT (abridged) Philosophical Transactions of the Royal Society 1665–1800 (abridged), London, 1809 - Andreev ₁ K. A. Andreev, On geometrical correspondences ... (in Russian), Moscow, 1879 - Andreev ₂ K. A. Andreev, On the Geometrical Formation of Plane Curves (in Russian), Kharkov, 1875     

Calcium and the contractile response to prostaglandin in the smooth muscle of guinea-pig stomach

Summary In the longitudinal smooth muscle of guinea-pig stomach, verapamil (10^–5 M) which showed marked suppression of high K-induced contractures, did not suppress the contractile response to PGE₁ (1.5×10^–9 to 10^–6 M) markedly. These results suggest that the contractile mechanism of PGE₁ in guinea-pig stomach may mainly depend on a release of bound Ca in the cell and partly depend on a Ca influx from the extracellular origin.     

Effect of prostaglandins on skin tumorigenesis

Summary Concomitant administration of prostaglandins E₂ (PGE₂) and F₂ a(PGF₂ a) with a carcinogen, 3-methylcholanthrene (MCA) to mice for 2 months markedly enhanced the occurrence of squamous cell carcinomas. Only epidermal cell hyperplasia occurred in mice treated with MCA alone by that time. Radioactivity measurements and electron microscopic autoradiography revealed that prostaglandins stimulate DNA, RNA and protein synthesis in neoplastic cells. These findings indicate that PGE₂ and PGF₂ a can act as cocarcinogens on skin tumorigenesis.     

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.     

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.     

Arachidonic acid signaling is involved in the mechanism of imidazoline-induced K<Subscript>ATP</Subscript> channel-independent stimulation of insulin secretion

The mechanism by which the novel, pure glucose-dependent insulinotropic, imidazoline derivative BL11282 promotes insulin secretion in pancreatic islets has been investigated. The roles of K_ATP channels, α₂-adrenoreceptors, the I₁-receptor-phosphatidylcholine-specific phospholipase (PC-PLC) pathway and arachidonic acid signaling in BL11282 potentiation of insulin secretion in pancreatic islets were studied. Using SUR1^(-/-) deficient mice, the previous notion that the insulinotropic activity of BL11282 is not related to its interaction with K_ATP channels was confirmed. Insulinotropic activity of BL11282 was not related to its effect on α₂-adrenoreceptors, I₁-imidazoline receptors or PC-PLC. BL11282 significantly increased [³H]arachidonic acid production. This effect was abolished in the presence of the iPLA₂ inhibitor, bromoenol lactone. The data suggest that potentiation of glucose-induced insulin release by BL11282, which is independent of concomitant changes in cytoplasmic free Ca²⁺ concentration, involves release of arachidonic acid by iPLA₂ and its metabolism to epoxyeicosatrienoic acids through the cytochrome P-450 pathway. Received 5 July 2007; received after revision 18 September 2007; accepted 20 September 2007     

Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages

Hydrogen sulfide (H₂S) plays an important role in inflammation. We showed that macrophages expressed the H₂S-forming enzyme cystathionine gamma-lyase (CSE) and produced H₂S. Lipopolysaccharide (LPS) stimulated the CSE expression and H₂S production rate. l-cysteine reduced LPS-induced nitric oxide (NO) production. CSE inhibitor blocked the inhibitory effect of l-cysteine. CSE knockdown increased, whereas CSE overexpression decreased LPS-induced NO production. Dexamethasone suppressed LPS-induced CSE expression and the H₂S production rate as well as NO production. l-arginine increased, whereas N^G-nitro-l-arginine methyl ester (l-NAME) decreased LPS-induced CSE expression and H₂S production. Dexamethasone plus l-NAME significantly decreased LPS-induced CSE expression and H₂S production compared to l-NAME. Our results suggest that macrophages are one of the H₂S producing sources. H₂S might exert anti-inflammatory effects by inhibiting NO production. Dexamethasone may directly inhibit CSE expression and H₂S production, besides the NO-dependent way. Inhibition of H₂S and NO production may be a mechanism by which glucocorticoids coordinate the balance between pro- and anti-inflammatory mediators during inflammation.     

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.     

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.     

Effects of disodium EDTA on the cardiovascular responses to prostaglandin E1

Zusammenfassung Die Wirkung des Dinatrium-EDTA auf die Kreislaufreaktionen des Prostaglandin E₁ (PGE₁) wurde an narkotisierten Hunden untersucht. Das Ausmass der positiv chronotropen und inotropen Einflüsse des PGE₁ war während der Infusion von EDTA bedeutend geringer als das des PGE₁ vor der EDTA-Gabe. Die Gegenwart oder das Einströmen von Kalziumionen scheint in der pharmakologischen Wirkung des PGE₁ eine Rolle zu spielen.     

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.