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

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.     

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.     

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.     

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.     

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.     

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.     

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     

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).     

The effects of prostaglandin E1 on the systemic and pulmonary circulations of intact dogs. The influence of urethane and pentobarbital anesthesia

Zusammenfassung Es wird gezeigt, dass Phenobarbital- und Urethan-Anästhesie nach Infusion von PGE₁ in den Kreislauf normaler Hunde verschiedene hämodynamische Reaktionen (Herzminutenvolumen, Herzfrequenz, Durchblutung der Peripherie) verursacht.Die Intrakoronarinfusion von PGE₁ mit der Narkose ergab einen negativ chronotropen und einen negativ inotropen Effekt.

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Supported by grants No. HE-06769 from the National Heart Institutes of the U.S. Public Health Service, the Rudolph Matas Memorial Fund for the Kate Prewitt Hess Laboratory and the Rowell A. Billups Fund for Research in Heart Disease.     

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.     

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.     

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).     

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.     

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 prostaglandin E1 on cholesterol biosynthesis in rat liver

Riassunto La prostaglandina E₁ (PGE₁) ha un duplice effetto sulla sintesi epatica del colesterolo: a basse concentrazioni determina un incremento della incorporazione di acetato in colesterolo, mentre a concentrazini superiori a 50 nmoli essa determina una riduzione di questo paramentro.     

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.     

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.     

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.     

Tricyclic antidepressants antagonize prostaglandin (PG) E20induced contractions of the guinea pig ileum and hypomotility in the mouse

Summary The interactions of PGE₂ and 2 tricyclic antidepressants were tested both on the guinea pig ileum and motility in the mouse. PGE₂-induced contractions of the guinea pig ileum were irreversibly blocked by amitriptyline and desipramine. Chronic administration of amitriptyline and desipramine blocked PGE₂-induced hypomotility in the mouse.     

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.