Effect of dexamethasone on in vivo prostanoid production in the rabbit.

Náray-Fejes-Tóth, Anikó; Fejes-Tóth, Géza; Fischer, Christine; Frölich, Jürgen C.

doi:10.1172/jci111391

Cited by 55 publications

(15 citation statements)

References 20 publications

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“…PGE 2 is the major prostaglandin synthesized along the rabbit nephron (1) and is a major urinary prostanoid (38). Intrarenal PGE infusion results in a natriuresis and diuresis, without significant changes in glomerular filtration rate, supporting its role as a natriuretic autacoid that modulates epithelial Na ϩ absorption (39).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor.

Guan¹,

Zhang²,

Breyer³

et al. 1998

J. Clin. Invest.

130

104

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PGE 2 exerts potent diuretic and natriuretic effects on the kidney. This action is mediated in part by direct inhibition of collecting duct Na ϩ absorption via a Ca ϩϩ -coupled mechanism. These studies examine the role the Ca ϩϩ -coupled PGE-E EP 1 receptor plays in mediating these effects of PGE 2 on Na ϩ transport. Rabbit EP 1 receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays demonstrated highest expression of EP 1 mRNA in kidney, followed by stomach, adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP 1 mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused rabbit cortical collecting duct, EP 1 active PGE analogs were 10-1,000-fold more potent in raising intracellular Ca ϩϩ than EP 2 , EP 3 , or EP 4 -selective compounds. Two different EP 1 antagonists, AH6809 and SC19220, completely blocked the PGE 2 -stimulated intracellular calcium increase. AH6809 also completely blocked the inhibitory effect of PGE 2 on Na ϩ absorption in microperfused rabbit cortical collecting ducts. These studies suggest that EP 1 receptor activation mediates PGE 2 -dependent inhibition of Na ϩ absorption in the collecting duct, thereby contributing to its natriuretic effects. ( J. Clin. Invest . 1998. 102:194-201.)

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor.

Guan¹,

Zhang²,

Breyer³

et al. 1998

J. Clin. Invest.

130

104

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“…Prostaglandin F 2␣ is a major prostaglandin excreted in urine (1) and is known to exert potent biological effects via its G protein-coupled cell membrane receptor designated the F-prostanoid (FP) 2 receptor (2-6). FP receptor mRNA is highly expressed along the genitourinary tract including ovary Ͼ uterus and kidney (7)(8)(9).…”

mentioning

confidence: 99%

Characterization of a Rabbit Kidney Prostaglandin F2α Receptor Exhibiting Gi-restricted Signaling That Inhibits Water Absorption in the Collecting Duct

Hébert

Carmosino

Saito

et al. 2005

Journal of Biological Chemistry

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PGF 2␣ is the most abundant prostaglandin detected in urine; however, its renal effects are poorly characterized. The present study cloned a PGF-prostanoid receptor (FP) from the rabbit kidney and determined the functional consequences of its activation. Nuclease protection assay showed that FP mRNA expression predominates in rabbit ovary and kidney. In situ hybridization revealed that renal FP expression predominates in the cortical collecting duct (CCD Prostaglandin F 2␣ is a major prostaglandin excreted in urine (1) and is known to exert potent biological effects via its G protein-coupled cell membrane receptor designated the F-prostanoid (FP) 2 receptor (2-6). FP receptor mRNA is highly expressed along the genitourinary tract including ovary Ͼ uterus and kidney (7-9). Recent studies in mouse kidneys have shown that FP receptor expression is particularly abundant in the distal convoluted tubules and cortical collecting duct (10). The cellular and functional consequences of renal FP receptor activation in these renal epithelia have not been determined. Like PGE 2 (11), intravenous infusion of PGF 2␣ causes both a natriuresis and diuresis (4); however, because high concentrations of PGF 2␣ can cross-activate prostaglandin E 2 -EP3 receptors (12, 13), the molecular basis of PGF 2␣ -associated diuresis remains uncertain. The functional activity of PGE 2 in the rabbit collecting duct epithelium has been elucidated through use of the in vitro microperfused tubule (9, 14 -16); however, the effect of selective FP receptor activation in this segment has not previously been examined. The aim of the present study was to clone the rabbit FP receptor, determine its intrarenal distribution, and elucidate its functional activity in the kidney.

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“…Almost all have been performed in animals. These experiments, with rare exception (5), have failed to demonstrate a suppressive effect (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), even in the face of unequivocal inhibition of eicosanoid formation in vitro (10). We have designed a study to evaluate the effects of therapeutic doses of glucocorticoids on the synthesis of eicosanoids in vivo in humans.…”

mentioning

confidence: 99%

Inhibition of eicosanoid biosynthesis by glucocorticoids in humans.

Sebaldt

Sheller

Oates

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

139

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Therapeutic doses of glucocorticoids are thought to inhibit prostaglandin and leukotriene formation in humans. Several studies in animals, however, have failed to demonstrate modulation of eicosanoid biosynthesis by steroids in vivo. We administered prednisone (60 mg/day) to eight healthy volunteers and measured eicosanoid formation by a variety of cell types in vivo and ex vivo, using sensitive and specific physicochemical assays. We found that the in vivo course of prednisone failed to inhibit the synthesis of thromboxane A2, prostaglandin 12 (prostacyclin), prostaglanin E2, and leukotriene E4 in vivo and of leukotriene B4 ex vivo. Biosynthesis of leukotriene B4, thromboxane B2, and prostaglandins F2 and E2 by macrophage-rich bronchoalveolar lavage cells was strongly suppressed. These findings indicate that therapeutic regimens of glucocorticoids suppress eicosanoid biosynthesis in human macrophages but not in a number of other cell types with steroid receptors, the capacity for eicosanoid formation, and lipocortin-like material. Study Design. In the 7-day study, the eight subjects took 60 mg of prednisone every morning by mouth for 7 days, the equivalent of 8 times the normal total daily production of hydrocortisone. On both of the 2 days immediately before drug treatment and again on both of the final 2 days of this course, heparinized (20 units/ml) whole blood and 24-hr urine collections were obtained. All blood samples were obtained at the same time of day, which at the end of the study was 2 hr after the preceding dose of prednisone. In four of these eight subjects, bronchoalveolar lavage was also performed, initially 1 week before the start and again at the end of the treatment. In the short-term study, the six subjects took 60 mg of prednisone by mouth at 0800 on two consecutive days. Twenty-four-hour urine collections were obtained before and on the first day of drug treatment and heparinized whole blood was obtained 0,1,2,4,8,24, and 30 hr after the first dose.Plasma prednisone and prednisolone concentrations were measured by HPLC (16). The completion of all urine collections obtained in the study was inferred from the close similarity of total creatinine in the four collections obtained from each subject. Prior to storage at -20°C, aliquots (5 ml)were equilibrated with stable-isotope-labeled standards.Whole blood leukocyte stimulation ex vivo was performed as described (17). Heparinized whole blood was divided into aliquots in polypropylene tubes and stimulants were added as follows: freshly opsonized zymosan A (100 and 250 ,ug/ml), the formylated tripeptide fMet-Leu-Phe (1 and 2 ,tM) in the presence of cytochalasin B (5 ttg/ml), anti-human IgE (1 and 2 ,g/ml), or no added stimulant (17). After incubation at 37°C in a shaking water bath for 30 min, the plasma was immediately collected by centrifugation and aliquots were equilibrated with 5 ng of 2H4-labeled LTB4. 6974The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby mark...

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Effect of dexamethasone on in vivo prostanoid production in the rabbit.

Cited by 55 publications

References 20 publications

Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor.

Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor.

Characterization of a Rabbit Kidney Prostaglandin F2α Receptor Exhibiting Gi-restricted Signaling That Inhibits Water Absorption in the Collecting Duct

Inhibition of eicosanoid biosynthesis by glucocorticoids in humans.

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