Increased blood pressure in the SHR is not related to a deficit in renomedullary PGE2

Summary Synthesis of prostaglandin E₂ by renal medulla from SHR and WKY rats was compared during early postnatal development. Although arterial blood pressure was significantly higher in SHR as early as 6 weeks of age, no difference in renal medullary prostaglandin synthesis was observed.Supported in part by a grant from the michigan Heart Association and NIH grant AM-10913.     

Effects of exchange transfusion with perfluorochemical emulsions on hepatic oxygen supply and blood flow in the rat

Summary Exchange-transfusion to hematocrit 20 with isotonic perfluorochemical (PFC) emulsions containing 3% hydroxyethylstarch (HES) in rats breathing 100% oxygen produced significant reductions of hepatic PO₂ and blood flow in comparison to rats hemodiluted with isotonic 3% or 6% HES solution. The results indicate that PFC and/or emulsifiers were associated with adverse effects on liver blood supply.This work was supported by a grant from the Kentucky Affiliate of the American Heart Association.     

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.     

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).     

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.     

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.     

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     

Deficiency in renomedullary prostaglandin synthesis related to the evolution of essential hypertension

Summary Continued PG synthesis in the early stages of essential hypertension might reflect an activation of the renal antihypertensive function in respect to neurogenic and/or hormonal pression stimuli, subsequently a deficiency of renal PG synthesis related to irreversible changes with the kidney would lead to the prepoderance of a pressure mechanism, resulting to a further increase of blood pressure.We thank Dr.J. R. Pike of the Upjohn Company, Kalamazoo Michigan, who kindly provided PGs. This work was supported by a grant from INSERM (ATP 17 No. of contract73547917) to Dr.Papanicolaou.     

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.     

The effect of renal hydrodynamics on immune complex deposition

Summary The role of renal hydrodynamics on renal deposition of immune complexes was evaluated in acute serum sickness. Using i.v. radiolabelled antigen in rabbits under a variety of hydrodynamic alterations, these studies suggested that although intrarenal hydrodynamics influence renal deposition of immune complexes factors other than intrarenal hydrostatic pressure may be important.Supported by grants in aid from the Rocky Mountain Kidney Foundation, Colorado Heart Association, USPHS No. GRS 5 SO1 RR 05357 and USPHS No. HD 04024.Dr. Ozawa is a fellow in Neprhology.This work was performed during the tenure of an Established Investigatorship from the American Heart Association (Dr.McIntosh).     

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.     

Imparied bone resorption of cultured calvaria from mice with abnormal lysosomal function (the Chediak-Higashi syndrome)

Summary Spontaneous bone resorption is reduced in cultured calvarial bones from mice with the Chediak-Higashi syndrome, as indicated by decreased mobilization of calcium from the bones to the medium. Although bone resorption in calvaria from mice with this disease can be stimulated by PGE₂ and 1 (OH)D₃, the amounts of mineral released after stimulation is also decreased.This investigation was supported by grants from the Swedish Association against Rheumatic Diseases, from the Royal 80 Year Fund of King Gustav V, and from the Swedish Medical Research Council (project No 14X-05426).     

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.     

Prostaglandin-like substances inPropionibacterium acnes. IV. Effect on isolated human vessels

Summary The present study demonstrates a powerful vasoconstrictor activity of prostaglandin-like substances (PLS), extracted fromP. acnes, on human blood vessels. PLS is about equipotent to PGE₂ in its effect on human umbilical vessels, but the contractile response pattern is different. PLS therefore seems to have specific and different physiological characteristics.     

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.     

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.     

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     

Influence of PGA1 on cartilage growth

Summary Using the Fell technique of organ culture of cartilage in a chemically defined medium, it has been shown that prostaglandin A₁ at a concentration of 25 g/ml caused chondrocyte death in chick embryonic limb rudiments. An equimolar concentration of PGE₂ was not toxic to the cells.Acknowledgments. We are grateful for the support of C. J. K. by the Medical Research Council and of D. L. G. by the Arthritis and Rheumatism Council for Research. Our thanks are due to Dame Honor Fell, F. R. S. for invaluable advice and guidance, to Dr J. Pike (Upjohn Co.) for supplies of prostaglandin A₁, and to Dr Sylvia Fitton-Jackson for the gift of culture medium.     

Cerebrovascular reactivity to CO2: Modulation by arterial pressure

Summary Cerebrovascular reactivity to CO₂ (CO₂R), measured in halothane-anesthetized rabbits, decreased as arterial pressure was increased either pharmacologically or mechanically. On the other hand, hypotension, induced by bleeding, led to an increase in CO₂R. These responses were unaffected by denervation of baroreceptors.This work was supported by grants from NIH (HL 17903) and American Heart Association — Greater Los Angeles Affiliate (437IG). To whom requests for reprints should be sent.