Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sites of synthesis and action of prostaglandins (PGs) along the renal tubule are examined. We focused our attention on experiments performed on well-defined nephron segments, using direct quantitative measurements of prostaglandin synthesis by radio- or enzyme-immunoassay. On the other hand, we selected, among the described effects of PGs, those obtained on precisely defined tubular segments. Among PGs, PGE2 synthesis is largely predominant all along the tubule. Its main sites of synthesis are the medullary collecting tubule and, to a lesser extent, the cortical collecting tubule and the thin limb of Henle's loop. Synthesis of PGE2 is amplified approximately tenfold in the presence of an excess exogenous substrate, arachidonic acid, compared with values measured without addition of substrate. Other eicosanoids have roughly the same distribution along the tubule as PGE2. Their rate of synthesis is, however, much less than that of PGE2, approximately 20-fold lower for PGF2 alpha and 6-keto-PGF1 alpha, and 100-fold lower for thromboxane B2 (TxB2). This contrasts with glomerular PG synthesis, where the difference between the production of PGE2 and other eicosanoids is much less marked. Most studies agree that antidiuretic hormone (ADH) and kinins augment PGE2 synthesis, whereas corticosteroids decrease it, at least in the collecting tubule. Direct effects of PGE2 have been described mainly in the medullary thick ascending limb and collecting tubule. They generally consist of a decrease in transepithelial potential difference and reabsorptive rates of water and solutes, in particular sodium and chloride. However, whatever the solute or tubular segment concerned, some studies failed to find such effects. The bulk of evidence suggests that ADH and PGs interact in kidney tubular cells. It is generally accepted that PGs antagonize the hydrosmotic effects of ADH in the collecting tubule. The mechanisms underlying these complex interactions are still under discussion: they probably involve several types of receptors and pathways for ADH action, which intervene in the modulation of both PG synthesis and cyclic nucleotides, and several types of PG receptors, either stimulatory or inhibitory to adenylate cyclase.
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PMID:Segmental synthesis and actions of prostaglandins along the nephron. 330 55

Glucocorticoids have been shown in in vitro systems to inhibit the release of arachidonic acid metabolites, namely prostaglandins (PGs) and leukotrienes, apparently, via the induction of a phospholipase A2 inhibitory protein, called lipocortin. On the basis of these in vitro results, it has been suggested that inhibition of eicosanoid production is, at least partially, responsible for the well-known anti-inflammatory effect of glucocorticoids. There is, however, no firm evidence proving that glucocorticoids also inhibit prostaglandin or leukotriene synthesis in vivo. In a series of studies, we have investigated the effects of anti-inflammatory steroids on the production of six different cyclo-oxygenase products in vivo. Urinary prostaglandin (PG) E2(1), PGF2 alpha, thromboxane B2 (TxB2), 6-keto-PGF1 alpha, and the major urinary metabolites of the E and F PGs, PGE-M and PGF-M, respectively, were determined by radioimmunoassay and by GC-MS. Administration of pharmacological doses of dexamethasone to rabbits failed to inhibit urinary excretion rates of PGE2, TxB2, 6-keto-PGF1 alpha and that of PGE-M and PGF-M. In contrast, urinary PGF2 alpha was slightly reduced by dexamethasone. In further experiments the effect of dexamethasone was studied in humans. Urinary excretion rates of PGE2, PGE-M, PGF-M, 2,3-dinor TxB2 and 2,3-dinor 6-keto-PGF1 alpha were not suppressed by dexamethasone. Collagen-induced platelet TxB2 formation and platelet aggregation was also unaltered. To test one possible explanation for the apparent discrepancy between in vitro and in vivo effects of glucocorticoids on arachidonic acid metabolites we investigated the effects of dexamethasone in vivo on basal and on antidiuretic hormone-stimulated renal PG synthesis. Dexamethasone treatment failed to inhibit both basal and antidiuretic hormone-stimulated PGE2 and PGF2 alpha production. We conclude that glucocorticoids in vivo do not decrease the basal rate of total body, kidney and platelet prostanoid synthesis, and that dexamethasone does not inhibit renal PG production when it is elevated by antidiuretic hormone, a physiological stimulus. Thus, a differential effect of glucocorticoids on basal vs stimulated PG synthesis cannot account for the discrepancy between in vivo and in vitro effects.
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PMID:Glucocorticoid effect on arachidonic acid metabolism in vivo. 338 43

The passive (lumen-to-bath) K+ permeation (KK) of rabbit cortical collecting tubules was measured before and after inhibition of Na+ transport. Inhibition of the Na-K pump with ouabain reduced KK. This result contrasts sharply with the previously described increase in KK observed following inhibition of Na+ transport with amiloride. These opposite changes in KK are owing to the fact that a substantial component of the lumen-to-bath K+ permeation involves a transcellular pathway. Amiloride, because it hyperpolarizes the apical membrane, increases KK; ouabain, because it depolarizes the cell, decreases KK. Previous results have also suggested that the cell K+ permeability is secondarily altered by these agents so that the changes in voltage and permeability are additive. These patterns of changes in KK were used to evaluate the mechanism of action of two agents that partially inhibit Na+ transport: vasopressin and prostaglandin (PG) E2. Their effect on KK was qualitatively similar to that of amiloride. In amiloride-treated tubules, neither vasopressin nor PGE2 altered KK. Neither did they alter the normal reduction in KK caused by pump inhibition. Thus they did not have any direct effect on K+ permeability. These results are consistent with the thesis that vasopressin and PGE2 inhibit Na+ absorption by reducing apical membrane permeability. The relation between the regulation of Na+ absorption and K+ permeation may have important implications for the regulation of K+ secretion by the cortical collecting tubule.
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PMID:Patterns of K+ permeation following inhibition of Na+ transport in rabbit cortical collecting tubule. 345

The compartmental effects of angiotensin II (AII) and arginine-vasopressin (AVP) on renal prostaglandin (PG) formation were studied in the isolated perfused kidney of the rabbit by superfusion bioassay of venous and ureteral effluents (VE and UE) and radioimmunoassay (RIA). Comparable results were obtained with either bioassay or RIA when used to quantitate renal PG release. The effects on PG release into the VE were similar for AII and AVP, as were their pressor responses. However, their effects on PG release into the UE differed markedly. AII resulted in a 6-fold greater urinary efflux than venous of bioassayable PGs, whereas AVP-induced PG release into UE was slightly less than PG efflux into the VE at all doses of the peptide. The profile of released PGs varied according to the sampling source (VE or UE). Moreover, each peptide released a similar profile of PGs at all doses, i.e. UE PGE2 greater than PGF2 alpha greater than 6-keto PGF1 alpha; VE PGE2 greater than 6-keto PGF1 alpha greater than PGF2 alpha (TxB2 was not detected in either effluent). Thus, renal vascular PG release is similar for the vasoactive peptides, AII and AVP, whereas the urinary efflux of PGs is considerably greater in response to AII.
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PMID:Compartmental prostaglandin release by angiotensin II and arginine-vasopressin in rabbit isolated perfused kidneys. 345 5

The hemodynamic effects of prostaglandins PGA1, PGE1, PGE2, and PGF2 alpha on the splanchnic circulation were evaluated in five chronic dogs with portal hypertension, periportal fibrosis, and portosystemic venous shunting. The maximum effect was achieved with dosages of 2 micrograms/kg/min after bolus injection into the superior mesenteric artery. With this dosage a monophasic increase of portal blood flow and pressure was found with PGA1, PGE1, and PGE2, whereas PGF2 alpha caused a biphasic response: an initial decrease in portal blood flow and pressure was followed by an increase in these parameters. The average peak increase in portal blood flow and pressure was similar for PGE1 and PGF2 alpha, and significantly smaller for PGA1 and PGE2. Average peak iodine concentrations in the portal blood after superior mesenteric angiography were highest with PGF2 alpha, similar for PGE1 and tolazoline, and lowest in controls. The vasoconstrictor effect of PGF2 alpha is, overall, reduced and less reproducible when compared with vasopressin. This investigation suggests that both PGE1 and PGF2 alpha are effective for improved arterial portography, the latter agent appearing superior. On the other hand, PGF2 alpha cannot be recommended as a therapeutic agent for the treatment for gastrointestinal and particularly variceal bleeding.
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PMID:Prostaglandins in diagnostic and therapeutic superior mesenteric artery pharmacoangiography. 345 97

Urinary excretion rates of PGE2 and PGF2 alpha were measured radioimmunologically in four different groups of unanaesthetized rats: water diuretic rats (I), rats with free access to water (II), water deprived rats (III) and 1.5% saline-loaded rats (IV). The animals were decapitated when steady states of urine formation were ascertained for three to six spontaneously delivered urine portions. Plasma vasopressin was measured radioimmunologically and urea, sodium, potassium concentrations and osmolalities of papillary fluids and of bladder urines were determined. Group means of urinary prostaglandin excretion, papillary urea concentration and logarithmic-transformed plasma vasopressin values vary in parallel for three of the groups (I, II and III) but a dissociation of the effects of papillary urea and vasopressin on the prostaglandin excretion was obtained for group IV. Statistical analyses indicated that the differences in prostaglandin excretion rates between group I and the three other groups are accounted for by the combined effects of vasopressin and papillary urea. The results support the hypothesis that vasopressin stimulates release of arachidonic acid in the papilla and that urea inhibits the trapping of this prostaglandin precursor in cellular lipids. The ratio of urinary PGF2 alpha to PGE2 varied greatly between groups but no consistent dependency on the measured parameters was found.
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PMID:The influence of renal papillary urea concentrations and of plasma vasopressin on the urinary prostaglandins E2 and F2 alpha excretion in conscious rats in steady state of urine formation. 345 52

The effect of vasopressin (VP) on prostaglandin (PG) synthesis in the renal collecting tubule remains equivocal. To further address this issue, the present study determined the effects of chronic absence of VP on renal medullary collecting tubule PG synthesis. Prostaglandin E2 (PGE2) synthesis was measured in both inner and outer medullary slices and collecting tubules microdissected from the inner medulla (PCD) and outer medulla (MCT) of Brattleboro homozygous diabetes insipidus (DI) rats, which are genetically devoid of VP, and from Long Evans (LE) control rats. In vitro PGE2 synthesis was significantly lower in both inner medullary (delta - 56%; p less than 0.001) and outer medullary (delta - 56%; p less than 0.01) slices of DI rats compared to controls. Vasopressin tannate treatment (0.5 U/day for 5 days) increased urinary PG excretion, and increased in vitro PGE2 synthesis in both inner and outer medullary slices of DI rats to levels that did not differ from vehicle-treated LE controls. In contrast, PGE2 synthesis in both PCD and MCT of DI rats did not differ from LE controls when incubated either in an isotonic (300 mOsm) medium, or in an hypertonic (1000 mOsm) medium. These results suggest that PGE2 biosynthetic capacity of medullary collecting tubules in the DI rat is not dependent on VP, while depressed PGE2 synthesis in renal medullary slices of DI rats, suggests that the interstitial cell is the primary medullary site of PG synthesis which is modulated by VP.
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PMID:Renal prostaglandin E2 synthesis in the Brattleboro homozygous diabetes insipidus rat. 345 94

The aim of the study was to investigate the urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), thromboxane B2 (TxB2; a stable metabolite of TxA2), and PGE2 in 18 normal subjects, 49 cirrhotics with ascites without renal failure (GFR = 90 +/- 4 ml/min, means +/- S.E.M.) and 20 cirrhotics with functional renal failure (FRF) (GFR = 36 +/- 3). The study was made after 5 days on a 50 mEq sodium diet and without diuretics. Plasma renin activity (PRA), plasma norepinephrine concentration (NE) and plasma antidiuretic hormone concentration (ADH) were also measured. Cirrhotics without FRF showed a significantly higher urinary excretion of 6-keto-PGF1 alpha, TxB2 and PGE, (15.9 +/- 1.7 ng/h, 3.0 +/- 0.3 ng/h, and 6.2 +/- 1.0 ng/h) than did normal subjects (9.2 +/- 0.9, 1.3 +/- 0.1 and 2.3 +/- 0.4). On the contrary, the urinary excretion of these prostaglandins was normal or reduced in patients with FRF (5.3 +/- 0.8, 1.3 +/- 0.2 and 1.9 +/- 0.4). PRA, NE and ADH were significantly increased in cirrhotics with FRF (15.2 +/- 3.9 ng/ml/h, 1026 +/- 149 pg/ml and 4.1 +/- 0.3 pg/ml) and in patients without FRF (8.0 +/- 1.4, 667 +/- 67 and 3.9 +/- 0.3) as compared to normal controls (1.3 +/- 0.2, 275 +/- 46 and 2.4 +/- 0.2). These results suggest that renal hemodynamics in cirrhosis depends upon a critical equilibrium between the activity of endogenous vasoconstrictor systems and the renal production of the vasodilator prostaglandins PGI2 and PGE2. In addition, they do not support FRF in cirrhosis being related to an increased renal production of the vasoconstrictor prostaglandin TxA2.
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PMID:Urinary excretion of 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 in cirrhosis with ascites. Relationship to functional renal failure (hepatorenal syndrome). 346 43

Increased urinary prostaglandin E excretion (UPGE2V) and renal production of PGE2 have been implicated in the mediation of escape from inappropriate antidiuresis induced by vasopressin (AVP). AVP-induced increases in PGE2 have been linked to its pressor activity. We examined the effects of the non-pressor AVP analogue, 1,desamino-8-D-arginine vasopressin (DDAVP), on UPGE2V in a rat model of inappropriate antidiuresis in which the escape response is not apparent. A dose of DDAVP known to cause antidiuresis (10 ng/hr), was given by osmotic minipump to rats during a water diuresis established by ad libitum ingestion of 5% dextrose in water (D/W). This dose of DDAVP reduced plasma sodium (P[Na+] ) to 127 +/- 2 mEq/liter within 24 hr. P[Na+] in controls given 5% D/W alone was 151 +/- 2. In the first eight hr after DDAVP, UPGE2V was fivefold higher than in control animals, an increase which was sustained for 48 hrs. Plasma renin (PRA) was threefold higher in control rats compared to rats that had received DDAVP, consistent with volume expansion in the latter. Despite declines in P[Na+] and PRA and increased UPGE2V in DDAVP treated rats, evidence of escape from inappropriate antidiuresis (secondary decline in Uosm or rise in urine volume (V) or P[Na+] ) was lacking. Moreover, DDAVP induced similar fivefold increases in UPGE2V when given to fluid deprived rats, demonstrating that increases of UPGE2V during inappropriate antidiuresis were not mediated by volume expansion. Administration of indomethacin to volume repleted DDAVP treated rats did not significantly increase Uosmol or decrease V compared to values observed in rats receiving DDAVP alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased urinary excretion of PGE2 during inappropriate antidiuresis induced by DDAVP. 346 22

In order to investigate the effects of changes in sodium (Na) balance on the renal production of prostaglandins (PG) E2 and F2 alpha in the absence of antidiuretic hormone (ADH), studies were performed in Brattleboro rats, without endogenous ADH, and in heterozygote Long Evans rats which served as controls. All rats received a diet virtually devoid of Na, with distilled water ad libitum, and Na intake was modified by adding different quantities of Na to the drinking water. Three groups were studied for each strain: normal Na intake, low Na intake and Na loading. At the end of a 14 day diet period, urinary PGE2 and PGF2 alpha were measured by radioimmunoassay in collections obtained for three consecutive days. In the Na depleted animals, both PGE2 and PGF2 alpha decreased. The PGE2/PGF2 alpha ratio (E/F ratio) was unchanged. In contrast, Na loading induced a significant decrease of PGE2 but PGF2 alpha increased, though not significantly. The E/F ratio was significantly decreased. The results were qualitatively similar in the presence or absence of ADH, but the Brattleboro rats, overall, excreted less PGs than controls. The results suggest that changes in Na balance are major factors influencing urinary PG excretion. These substances probably play a role in the modifications of Na handling by the kidney in different balance states.
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PMID:Sodium intake as a determinant of urinary prostaglandin excretion. Studies in the Brattleboro rat. 346 21


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