Involvement of prostaglandin E2, cAMP, and vasopressin in lithium-induced polyuria

1988 ◽  
Vol 254 (6) ◽  
pp. R863-R869 ◽  
Author(s):  
M. Sugawara ◽  
K. Hashimoto ◽  
Z. Ota
Keyword(s):  
Prostaglandin E2 ◽  
Rat Kidney ◽  
Urine Volume ◽  
Renal Medulla ◽  
Pge2 Production ◽  
Camp Production ◽  
Vasopressin Release ◽  
Pge2 Synthesis ◽  
Plasma Vasopressin

The involvement of prostaglandin E2 (PGE2), adenosine 3',5'-cyclic monophosphate (cAMP), and vasopressin in lithium-induced polyuria was investigated in rats. Administration of LiCl (4 mmol/kg body wt) for 7 days induced a marked polyuria with a significant excretion of urinary PGE2. Administration of indomethacin (IND, 5 mg/kg body wt) for 4 days to lithium-induced diabetes insipidus (LiDI) rats diminished urine volume by 80% and urinary PGE2 by 85%. The in vitro data of the intact rat kidney showed that lithium stimulated arginine vasopressin (AVP)-induced PGE2 production and suggested that PGE2 suppressed cAMP synthesis in rat renal medulla. The AVP-induced PGE2 synthesis was greater and the AVP-stimulated cAMP production lower in the LiDI rat kidney in vitro. Interference of the vasopressin-associated cAMP system and the increased PGE2 synthesis in the kidney may be involved in the development of LiDI. The reduced cAMP production in the LiDI rat kidney might be partly due to the increased PGE2 synthesis. In LiDI rats plasma vasopressin increased, whereas AVP concentration in the hypothalamus and the neurohypophysis significantly decreased. It is postulated that lithium stimulates vasopressin release from the central nervous system and that elevated plasma vasopressin potentiates PGE2 production in the kidney synergistically with lithium.

Synthesis of prostaglandin E2 in different segments of isolated collecting tubules from adult and neonatal rabbits

1985 ◽  
Vol 248 (1) ◽  
pp. F134-F144 ◽  
Author(s):  
D. Schlondorff ◽  
J. A. Satriano ◽  
G. J. Schwartz
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Feedback Loop ◽  
Pge2 Production ◽  
Large Variability ◽  
Pge2 Synthesis ◽  
Collecting Tubule ◽  
Concentrate Urine ◽  
Collecting Tubules

Prostaglandin E2 (PGE2) inhibits the action of the antidiuretic hormone (ADH) in isolated collecting tubules. A negative feedback loop has been postulated whereby ADH stimulates PGE2 synthesis. Furthermore, lysyl-bradykinin (LBK) inhibits the antidiuretic effect of ADH, probably via PGE2. Enhanced PGE2 synthesis has also been implicated as contributing to the inability to maximally concentrate urine during the neonatal period. We investigated PGE2 synthesis in microdissected cortical (CCT), medullary (MCT), and branched cortical (BCT) collecting tubules from adult and in corticomedullary collecting tubules (CT) from newborn rabbits. Isolated BCT produced significantly less PGE2 (12 +/- 2 pg X mm-1 X 20 min-1) than CCT (65 +/- 9) or MCT (76 +/- 8) from kidneys of adult rabbits. CT from newborn rabbits produced only 19 +/- 3 pg/mm, significantly less than either CCT or MCT from adults. A large variability in basal PGE2 production and hormonal response was observed from tubule to tubule. Under either basal conditions or in the presence of 2 microM arachidonic acid, LBK enhanced PGE2 synthesis in CCT and MCT from adults. ADH enhanced PGE2 production in MCT under basal conditions and in CCT in the presence of arachidonic acid. Neither LBK nor ADH stimulated PGE2 synthesis in neonatal CT. A23187 consistently stimulated PGE2 synthesis in CCT and MCT from adults and, to a lesser extent, in CT from newborn rabbits. Our results support the hypothesis that ADH and LBK enhance PGE2 synthesis in the collecting tubule. This response is, however, subject to large variations from tubule to tubule and depends on the in vitro incubation conditions.

Thromboxane B2 and prostaglandin E2 in the rat kidney with unilateral ureteral obstruction

1982 ◽  
Vol 242 (3) ◽  
pp. F220-F225 ◽  
Author(s):  
M. A. Whinnery ◽  
J. O. Shaw ◽  
N. Beck
Keyword(s):  
Prostaglandin E2 ◽  
Ureteral Obstruction ◽  
Rat Kidney ◽  
Thromboxane A2 ◽  
Unilateral Ureteral Obstruction ◽  
Thromboxane B2 ◽  
Pge2 Production ◽  
Rabbit Kidney ◽  
Pharmacological Stimulation

The production of prostaglandin E2- (PGE2) like and thromboxane A2-(TXA2) like substances is increased after release of unilateral ureteral obstruction (UUO) for 3 days in the isolated perfused rabbit kidney. It has been postulated that this increase in TXA2 biosynthesis might contribute to the development of vasoconstriction in the obstructed kidney. In the present studies, the production of TXA2 and PGE2 in the kidney was further investigated in rats after UUO for 2-18 h. Radioimmunoassay was used to determine thromboxane B2 (TXB2), a chemically stable metabolite of TXA2, and PGE2 production during the incubation of renal slices in vitro. Unlike previous studies, an increase in TXB2 and PGE2 production was demonstrable in the obstructed kidney even in the absence of pharmacological stimulation by bradykinin or angiotensin II. The effect of UUO on prostaglandin production differed in the different anatomical parts of the kidney. In the papilla, production of both TXB2 and PGE2 was increased in the obstructed kidney. In the cortex, however, UUO had a stimulatory effect only on TXB2 production but not on PGE2 production. The increase in TXB2 and PGE2 production was demonstrable as early a 2 h (tested) after ureteral obstruction. Prolongation of ureteral obstruction for 18 h diminished the stimulatory effect of UUO on PGE2 production but not on TXB2 production.

Vasoconstriction of outer medullary vasa recta by angiotensin II is modulated by prostaglandin E2

1994 ◽  
Vol 266 (6) ◽  
pp. F850-F857 ◽  
Author(s):  
T. L. Pallone
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Hydraulic Pressure ◽  
Vascular Bundles ◽  
Ang Ii ◽  
Vasa Recta ◽  
Anatomical Arrangement

Vasa recta were dissected from outer medullary vascular bundles in the rat and perfused in vitro. Examination by transmission electron microscopy reveals them to be only outer medullary descending vasa recta (OM-DVR). To establish a method for systematic examination of vasoconstriction, OMDVR were perfused at 5 nl/min with collection pressure increased to 5 mmHg. Under these conditions, transmembrane volume flux was found to be near zero, and the transmural hydraulic pressure gradient was found to be < 15 mmHg. Over a concentration range of 10(-12) to 10(-8) M, abluminal application of angiotensin II (ANG II) caused graded focal vasoconstriction of OMDVR that is blocked by saralasin. Luminal application of ANG II over the same concentration range was much less effective. Abluminal application of prostaglandin E2 (PGE2) shifted the vasoconstrictor response of OMDVR to higher ANG II concentrations. PGE2 reversibly dilated OMDVR that had been preconstricted by ANG II. These results demonstrate that OMDVR are vasoactive segments. Their anatomical arrangement suggests that they play a key role in the regulation of total and regional blood flow to the renal medulla.

Phospholipids, prostaglandin E2, and proteolysis in denervated muscle

1986 ◽  
Vol 251 (1) ◽  
pp. R165-R173 ◽  
Author(s):  
J. Turinsky
Keyword(s):  
Protein Synthesis ◽  
Prostaglandin E2 ◽  
Pge2 Production ◽  
Nerve Transection ◽  
Denervated Muscle ◽  
Sciatic Nerve Transection ◽  
Tissue Protein ◽  
Pge2 Release ◽  
Denervated Muscles

Soleus muscles of rats were studied up to 16 days after sciatic nerve transection. At the end of this period the denervated soleus muscles exhibited decreased content of diphosphatidylglycerol (-44%), normal level of phosphatidylethanolamine, and increased contents of phosphatidylcholine (+24%), sphingomyelin (+48%), lysophosphatidylcholine (+110%), phosphatidylinositol (+37%), and phosphatidylserine (+40%) per milligram of tissue protein. In studies in vitro, prostaglandin E2 (PGE2) release and tyrosine release by denervated soleus muscles were 319 and 141%, respectively, greater than those of sham muscles. An almost complete inhibition of PGE2 release with 5 X 10(-4) M aspirin or 2.8 X 10(-6) M indomethacin had no effect on tyrosine release of sham muscles or the stimulated tyrosine release of the denervated muscles. Addition of 5 X 10(-5) M cycloheximide in the medium resulted in 63% inhibition of PGE2 release by both groups of muscles; concomitant absolute increments in tyrosine releases by denervated and sham muscles did not statistically differ. In the presence of both 5 X 10(-5) M cycloheximide and 5 X 10(-4) M aspirin in the medium, PGE2 production by denervated and sham muscles was inhibited 87% while tyrosine release of denervated muscles was 108% higher than that of sham animals. It is concluded that 1) atrophy of denervated soleus muscle is associated with stimulated activity of tissue phospholipase A2, increased production of prostaglandin E2, increased total proteolytic rate, and unchanged rate of protein synthesis; 2) acute inhibition of PGE2 production does not inhibit the stimulated proteolysis in denervated muscle; and 3) cycloheximide inhibits PGE2 production by muscle.

Endocytosis by cultured mesangial cells and associated changes in prostaglandin E2 synthesis

1987 ◽  
Vol 252 (4) ◽  
pp. F627-F634
Author(s):  
P. C. Singhal ◽  
G. H. Ding ◽  
S. DeCandido ◽  
N. Franki ◽  
R. M. Hays ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cytochalasin B ◽  
Mesangial Cells ◽  
Pge2 Production ◽  
Receptor Interaction ◽  
Coated Pits ◽  
Pge2 Synthesis ◽  
Gold Particles ◽  
Fresh Serum ◽  
Stimulation Of

The mechanism of macromolecule uptake by cultured mesangial cells was studied by use of transmission electron microscopy. In parallel, we investigated the effect of macromolecular uptake on prostaglandin E2 (PGE2) formation. Cultured rat mesangial cells were studied in their third passage. As model molecules, we used colloidal gold particles (10 nm diameter) coated either with polyethylene glycol (PEG) or fresh serum (SCG). Mesangial cells were incubated from 1 to 60 min and up to 12 h with either PEG or SCG particles. Endocytosis of SCG significantly exceeded that of PEG particles. The mechanism involved binding to coated pits, followed by formation of coated vesicles (endosomes), and eventually delivery of particles to lysosomes. Pretreatment with cytochalasin B virtually prevented endocytosis of SCG particles, indicating active participation of the cytoskeleton. Determination of PGE2 production in parallel showed that SCG significantly stimulated PGE2 synthesis within minutes, whereas PEG-coated gold had no effect. When gold particles were coated with decomplemented serum instead of fresh serum, the stimulation of PGE2 was partially, but not completely, prevented, indicating that complement may be one, but not the only ligand responsible for enhanced PGE2 production. Stimulation of PGE2 synthesis by SCG was not dependent on actual endocytosis, as it was not altered by cytochalasin B pretreatment. Thus, surface ligand-receptor interaction may be sufficient to trigger PGE2 synthesis. The interaction between mesangial endocytosis and PGE2 production may be important for glomerular pathophysiology.

Tubular prostaglandin E2 production and its role in urinary hypotonicity after release of ureteral occlusion in the rat

1987 ◽  
Vol 73 (4) ◽  
pp. 395-399 ◽  
Author(s):  
Shozo Torikai
Keyword(s):  
Prostaglandin E2 ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Pge2 Production ◽  
Endogenous Prostaglandin ◽  
Collecting Ducts ◽  
Ureteral Occlusion

1. In order to explore the involvement of endogenous prostaglandin E2 (PGE2) in the urine concentration defect after ureteral occlusion, PGE2 production by isolated collecting ducts in vitro and effects of indomethacin on urine osmolality in vivo were examined. 2. Twenty-four hours ureter obstruction caused increased PGE2 production by the medullary collecting ducts, which was maintained at a high level on the day after release of obstruction (0.8 ± 0.2 pg/mm normal, 8.1 ± 0.9 pg/mm 24 h obstruction, and 6.6 ± 1.0 pg/mm post-obstruction, mean ± sem). An enhanced PGE2 production was also observed for papillary collecting duct on the day after release of 24 h ureteral occlusion (3.9 ± 0.5 pg/mm normal and 7.7 ± 1.2 pg/mm post-obstruction). 3. Administration of indomethacin to the unilateral post-obstructive rats slightly raised the urine osmolality of the post-obstructed kidney (from 339 ± 17 to 390 ± 22 mosmol/kg H2O), while it had a greater effect on the contralateral intact kidney (from 1569 ± 138 to 2567 ± 198 mosmol/kg H2O). 4. Our data may indicate that the urine concentration defect after 24 h ureteral occlusion is ascribable mainly to a mechanism other than increased endogenous PGE2.

scholarly journals Low Salt Delivery Triggers Autocrine Release of Prostaglandin E2 From the Aldosterone-Sensitive Distal Nephron in Familial Hyperkalemic Hypertension Mice

2022 ◽  
Vol 12 ◽  
Author(s):  
Ava M. Zapf ◽  
Paul R. Grimm ◽  
Lama Al-Qusairi ◽  
Eric Delpire ◽  
Paul A. Welling
Keyword(s):  
Prostaglandin E2 ◽  
Cell Model ◽  
Kidney Cortex ◽  
Distal Nephron ◽  
Pge2 Synthesis ◽  
Low Salt ◽  
Model Mouse ◽  
Reduced Salt ◽  
Familial Hyperkalemic Hypertension

Aberrant activation of with-no-lysine kinase (WNK)-STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) kinase signaling in the distal convoluted tubule (DCT) causes unbridled activation of the thiazide-sensitive sodium chloride cotransporter (NCC), leading to familial hyperkalemic hypertension (FHHt) in humans. Studies in FHHt mice engineered to constitutively activate SPAK specifically in the DCT (CA-SPAK mice) revealed maladaptive remodeling of the aldosterone sensitive distal nephron (ASDN), characterized by decrease in the potassium excretory channel, renal outer medullary potassium (ROMK), and epithelial sodium channel (ENaC), that contributes to the hyperkalemia. The mechanisms by which NCC activation in DCT promotes remodeling of connecting tubule (CNT) are unknown, but paracrine communication and reduced salt delivery to the ASDN have been suspected. Here, we explore the involvement of prostaglandin E2 (PGE2). We found that PGE2 and the terminal PGE2 synthase, mPGES1, are increased in kidney cortex of CA-SPAK mice, compared to control or SPAK KO mice. Hydrochlorothiazide (HCTZ) reduced PGE2 to control levels, indicating increased PGE2 synthesis is dependent on increased NCC activity. Immunolocalization studies revealed mPGES1 is selectively increased in the CNT of CA-SPAK mice, implicating low salt-delivery to ASDN as the trigger. Salt titration studies in an in vitro ASDN cell model, mouse CCD cell (mCCD-CL1), confirmed PGE2 synthesis is activated by low salt, and revealed that response is paralleled by induction of mPGES1 gene expression. Finally, inhibition of the PGE2 receptor, EP1, in CA-SPAK mice partially restored potassium homeostasis as it partially rescued ROMK protein abundance, but not ENaC. Together, these data indicate low sodium delivery to the ASDN activates PGE2 synthesis and this inhibits ROMK through autocrine activation of the EP1 receptor. These findings provide new insights into the mechanism by which activation of sodium transport in the DCT causes remodeling of the ASDN.

scholarly journals Oxygen-dependent expression of hypoxia-inducible factor-1α in renal medullary cells of rats

2001 ◽  
Vol 6 (3) ◽  
pp. 159-168 ◽  
Author(s):  
AI-PING ZOU ◽  
ZHI-ZHANG YANG ◽  
PIN-LAN LI ◽  
ALLEN W. COWLEY
Keyword(s):  
Transcription Factor ◽  
Renal Cortex ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Hypoxia Inducible Factor ◽  
Renal Medulla ◽  
Hypoxia Inducible Factor 1Α ◽  
Nuclear Extracts ◽  
Medullary Cells

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates the oxygen-dependent expression of a number of genes. This transcription factor may contribute to the abundant expression of many genes in renal medullary cells that function normally under hypoxic conditions. The present study was designed to determine the characteristics of HIF-1α cDNA cloned from the rat kidney and the expression profile of HIF-1α in different kidney regions and to explore the mechanism activating or regulating HIF-1α expression in renal medullary cells. A 3,718-bp HIF-1α cDNA from the rat kidney was first cloned and sequenced using RT-PCR and TA cloning technique. It was found that 823 amino acids deduced from this renal HIF-1α cDNA had 99%, 96%, and 90% identity with rat, mouse, or human HIF-1α deposited in GenBank, respectively. The 3′-untranslated region of HIF-1α mRNA from the rat kidney contained seven AUUUA instability elements, five of which were found to be conserved among rat, mouse, and human HIF-1α. Northern blot analyses demonstrated a corticomedullary gradient of HIF-1α mRNA expression in the kidney, with the greatest abundance in the renal inner medulla. Western blot analyses also detected a higher HIF-1α protein level in the nuclear extracts from the renal medulla than the renal cortex. A classic loop diuretic, furosemide (10 mg/kg ip), markedly increased renal medullary Po2 levels from 22.5 to 52.2 mmHg, which was accompanied by a significant reduction of HIF-1α transcripts in renal medullary tissue. In in vitro experiments, low Po2, but not elevated osmolarity, was found to significantly increase HIF-1α mRNA in renal medullary interstitial cells and inner medullary collecting duct cells. These results indicate that HIF-1α is more abundantly expressed in the renal medulla compared with the renal cortex. Increased abundance of HIF-1α mRNA in the renal medulla may represent an adaptive response of renal medullary cells to low Po2.

Effects of atrial natriuretic peptide on renal medullary prostaglandin E2 production

1989 ◽  
Vol 257 (3) ◽  
pp. F336-F340
Author(s):  
R. J. Bolterman ◽  
M. D. Bentley ◽  
S. M. Sandberg ◽  
M. J. Fiksen-Olsen ◽  
J. C. Romero
Keyword(s):  
Arachidonic Acid ◽  
Atrial Natriuretic Peptide ◽  
Prostaglandin E2 ◽  
Natriuretic Peptide ◽  
Inhibitory Effect ◽  
Pge2 Production ◽  
In Vitro Effects ◽  
Different Doses ◽  
Atrial Natriuretic

Like arachidonic acid (AA) and bradykinin (BK), the intrarenal administration of atrial natriuretic peptide (ANP) has been shown to increase the urinary excretion of prostaglandin E2 (PGE2). In the present study, the direct in vitro effects of ANP on PGE2 production were compared with those of AA and BK. Canine renal inner medullary slices were preincubated for 30 min and washed in aerated Krebs-Ringer buffer (37 degrees C). During the final incubation period, with the use of varied concentrations of AA, BK, or ANP in Krebs-Ringer buffer, samples were obtained at 0 and 30 min to be used for radioimmunoassay of PGE2. Although the rate of PGE2 production was significantly increased 11-fold with AA and threefold with BK, it was unaffected by four different doses of ANP (10(-5) to 10(-11) M). Furthermore, the production of PGE2 during basal and stimulated (BK or AA) conditions was significantly blocked by indomethacin but not by ANP. These results indicate that ANP had no direct stimulatory or inhibitory effect on the medullary production of PGE2.

scholarly journals Interleukin-12 (IL-12) Production in Whole Blood Cultures From Human Immunodeficiency Virus-Infected Individuals Studied in Relation to IL-10 and Prostaglandin E2 Production

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 570-576 ◽  
Author(s):  
Linde Meyaard ◽  
Egbert Hovenkamp ◽  
Nadine Pakker ◽  
Tineke C.T.M. van der Pouw Kraan ◽  
Frank Miedema
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Prostaglandin E2 ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Blood Cultures ◽  
Pge2 Production ◽  
Interleukin 12 ◽  
Immunodeficiency Virus

Abstract The role of interleukin-12 (IL-12) in Th1 cell differentiation is well established. The heterodimer p70, composed of a p40 and a p35 chain, is the biologically active form. IL-12 production by human monocytes is enhanced by interferon-γ (IFN-γ) and inhibited by IL-10 and prostaglandin E2 (PGE2 ). Peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected individuals reportedly have impaired IL-12 p40 and p70 production on stimulation with Staphylococcus aureus Cowan I (SAC) in vitro. Both PGE2 and IL-10 previously were proposed to be instrumental in this defect in IL-12 production. Here, we studied IL-12 p40 and p70 production in relation to IL-10 and PGE2 production in whole blood cultures from HIV-infected individuals. On stimulation with lipopolysaccharide, IL-12 production was normal. However, on stimulation with SAC, IL-12 p40 and p70 production was decreased in HIV-infected individuals and correlated significantly with decreased peripheral blood CD4+ T-cell number and T-cell reactivity to CD3 monoclonal antibody in vitro. However, IL-10 and PGE2 production in cultures from HIV-infected individuals was normal and did not relate to IL-12 production. In conclusion, IL-12 production by cells from HIV-infected individuals is impaired under certain conditions in vitro and this decrease is independent of IL-10 or PGE2 production.

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