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)

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.
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PMID:Prostaglandins and the kidney. 33 46

We have reported that dopamine (DA) inhibits Na-K-ATPase activity in the cortical collecting duct (CCD) by stimulating the DA1 receptor, and the present study was designed to evaluate the mechanism of this effect. Short-term exposure (15-30 min) of microdissected rat CCD to DA, a DA1 agonist (fenoldopam), vasopressin (AVP), forskolin, or dibutyryl cAMP (dBcAMP), which increase cAMP content by different mechanisms, strongly (approximately 60%) inhibited Na-K-ATPase activity. 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, completely blocked Na-K-ATPase inhibition by DA or fenoldopam, and IP20, an inhibitor peptide of cAMP-dependent protein kinase A (PKA), abolished the Na:K pump effect of all the cAMP agonists listed above. To verify whether the mechanism of pump inhibition by agents that increase cell cAMP involves phospholipase A2 (PLA2), we used mepacrine, a PLA2 inhibitor, which also abolished Na-K-ATPase inhibition by DA or fenoldopam, as well as by AVP, forskolin, or dBcAMP. Arachidonic acid (10(-7) - 10(-4) M) inhibited Na-K-ATPase activity in dose-dependent fashion. Corticosterone, which induces lipomodulin, a PLA2 inhibitor protein inactivated by PKA, equally abolished the pump effects of DA, fenoldopam, forskolin, and dBcAMP, suggesting that lipomodulin might act between PKA and PLA2 in cAMP-dependent pump regulation. We conclude that dopamine inhibits Na-K-ATPase activity in the CCD through a DA1 receptor-mediated cAMP-PKA pathway that involves the stimulation of PLA2 and arachidonic acid release, possibly mediated by inactivation of lipomodulin. This pathway is shared by other agonists that increase cell cAMP and thus stimulate PKA activity.
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PMID:Intracellular signaling in the regulation of renal Na-K-ATPase. I. Role of cyclic AMP and phospholipase A2. 134 27

Arachidonic acid (AA) is reported to be metabolized by three major pathways, i.e., cyclooxygenase (CO), lipoxygenase (LO), and NADPH-dependent cytochrome P450 monooxygenase (MO) pathways. Monooxygenase metabolites of AA have been proposed to play an important role in hormone action in various cells. Recently it was reported that the MO pathway may exist in rat liver. The present study was carried out to investigate the role of MO metabolites in vasopressin-induced glycogenolysis in isolated rat hepatocytes. The pretreatment of isolated rat hepatocytes with eicosatetraynoic acid (ETYA), an inhibitor of CO, LO, and MO pathways, and ketoconazole and SKF 525A, inhibitors of the MO pathway, dose-dependently reduced vasopressin-induced phosphorylase activation, while the pretreatment with indomethacin, an inhibitor of the CO pathway, had no effect. The increment of cytosolic calcium concentration in vasopressin-stimulated hepatocytes was also dose-dependently decreased by ETYA, ketoconazole, and SKF 525A. In vitro addition of epoxyeicosatrienoic acid (EET) dose-dependently increased both phosphorylase a activity and cytosolic calcium concentration. 14,15-EET was the most potent among four regioisomeric EETs. These results suggest that MO metabolites of AA, most likely EETs, may be involved in vasopressin-induced glycogenolysis probably via the activation of phosphorylase by increasing the cytosolic calcium concentration.
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PMID:Possible involvement of arachidonic acid metabolites of cytochrome P450 monooxygenase pathway in vasopressin-stimulated glycogenolysis in isolated rat hepatocytes. 236 26

PGI2, or prostacyclin, and PGE2 are major derivatives of arachidonic acid. Arachidonic acid is converted by the cyclooxygenase enzyme to intermediate prostaglandin endoperoxides which are then enzymatically converted to PGI2 and PGE2 as well as to thromboxane A2 and PGF2 alpha. Aspirin and other nonsteroidal anti-inflammatory drugs inhibit the cyclooxygenase enzyme thereby reducing the amount of PGE2 and PGI2 produced. In the kidney, major stimuli of prostaglandin synthesis include vasoconstrictor hormones such as angiotensin II, vasopressin, endothelin and norepinephrine. Renal PGI2 and PGE2 synthesis is also increased after renal ischemia, immune injury to the kidney, and with renal parenchymal disease. Renal prostaglandin production also increases with severe arteriosclerotic cardiovascular disease, congestive heart failure, and severe hepatic disease. The increment of renal prostaglandin synthesis is important since PGI2 and PGE2 act as modulators of renal ischemia and vasoconstriction. The modulatory action leads to a negative feedback loop through which PGE2 and PGI2 and renal blood vessels in glomeruli reduce the vasoconstrictor action of the agonist, such as angiotensin II or norepinephrine. Nonsteroidal anti-inflammatory drugs can have nephrotoxic effects if they are used in clinical situations in which renal prostaglandin synthesis has increased compensatorily. In other words, the administration of indomethacin or other prostaglandin inhibitory drugs will reduce renal blood flow and glomerular filtration rate in patients with congestive heart failure, significant hepatic disease, or renal ischemia and vasoconstriction. PGI2 and PGE2 may have additional beneficial effects within the kidney in addition to being vasodilatory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin I2 and the kidney. 251 64

In addition to cAMP-dependent mechanisms, stimulation of pituitary ACTH secretion by various stimuli, including CRF, may involve phospholipid and arachidonic acid turnover. To determine the role of phospholipase A2 activation in corticotroph function, we studied the effect of exogenous arachidonic acid, phospholipase A2, and the phospholipase A2 activator melittin on ACTH release in cultured rat anterior pituitary cells. Incubation with 1-100 micron arachidonic acid, 0.01-1 micron melittin, 0.1-10 U/ml phospholipase A2, and 0.01-10 nM CRF caused dose-dependent increases in ACTH release to 8.1 +/- 1.1- (+/- SE), 16.2 +/- 0.9-, 13.6 +/- 1.2-, and 2.9 +/- 0.3-fold; respectively. The participation of the major pathways of arachidonic acid metabolism in the control of ACTH release was analyzed in cells treated with nordihydroguaiaretic acid, a lipoxygenase inhibitor; indomethacin, a cycloxygenase inhibitor; and 5,8,11,14-eicosatetraynoic acid, an inhibitor of both pathways. The effects of arachidonic acid, melittin, and CRF were partially blocked by 10 micron nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid, but were significantly enhanced by 10 micron indomethacin. These results suggest that arachidonic acid is mainly metabolized through the lipoxygenase pathway to a stimulatory metabolite and, to a lesser extent, through the cycloxygenase pathway to an inhibitory metabolite. Arachidonic acid release from anterior pituitary cells labeled with [3H]arachidonic was analyzed during cell column perifusion and stimulation by CRF and other secretagogues. Two-minute pulses of CRF (10 nM), vasopressin (10 nM) and phorbol 12-myristate 13-acetate (100 nM) caused immediate 1.5- to 2-fold increases in [3H]arachidonic acid release, and melittin (100 nM) caused a 5-fold increase in [3H]arachidonic acid release. The ability of both exogenously added and endogenously generated arachidonic acid to stimulate ACTH secretion, together with the stimulation of arachidonic acid release by ACTH secretagogues and the attenuation of stimulated ACTH release by lipoxygenase blockers, indicate that lipoxygenase products of arachidonic acid metabolism participate in the control of ACTH secretion.
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PMID:Role of arachidonic acid in the regulation of adrenocorticotropin release from rat anterior pituitary cell cultures. 301 33

To evaluate the hypothesis that prostaglandins (PGs) inhibit vasopressin stimulation of adenylate cyclase in the collecting tubule, we have studied the interactions of vasopressin, PGs, and intracellular cAMP in rat renal papillary collecting tubule (RPCT) cells in cell culture. Inhibition of PGE2 synthesis with acetylsalicylic acid (ASA) did not potentiate arginine vasopressin (AVP)-stimulated intracellular cAMP. Augmentation of prostanoid synthesis with arachidonic acid or exogenous addition of PGE2 did not decrease AVP-stimulated cAMP in the RPCT cells. Arachidonic acid or PGE2, used alone, increased cAMP and ASA reduced cAMP, consistent with the presence of a PG-sensitive adenylate cyclase. Six-hour incubations of RPCT cells produced clear evidence of homologous desensitization of the PGE2 receptor, after exposure to either PGE2 or arachidonic acid, but not heterologous desensitization of the AVP receptor linked to cAMP synthesis. Preincubation of the RPCT cells with AVP or 1-desamino-8-D-arginine vasopressin (dDAVP) induced homologous desensitization of AVP- or dDAVP-stimulated cAMP. Three-day incubations with dDAVP or AVP apparently induced cyclooxygenase activity since PGE2 synthesis increased in response to arachidonic acid and recovery of cyclooxygenase activity after ASA was enhanced by dDAVP or AVP. In conclusion, our data on AVP-stimulated cAMP in cultured RPCT cells do not support the hypothesis that PGE2 inhibits AVP-dependent collecting tubule cAMP.
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PMID:Interactions of vasopressin, prostaglandins, and cAMP in rat renal papillary collecting tubule cells in culture. 608 89

Although intrarenal infusions of kinins produce diuresis, it is not clear to what extent this response is due to hemodynamically mediated medullary washout and/or to direct epithelial effects of kinins. Recent evidence has shown that bradykinin binds to collecting tubules in vitro. We therefore examined the interactions of lysyl-bradykinin and antidiuretic hormone (ADH) with respect to hydraulic conductivity (Lp) in the rabbit cortical collecting tubule perfused in vitro. To ensure adequate substrate for prostaglandin synthesis, the bath contained 2.5 microM arachidonic acid. Arachidonic acid produced no change in base-line Lp and had no effect on the subsequent response to a supramaximal dose of ADH (100 microU/ml). Therefore, all subsequent experiments were done in the presence of arachidonic acid. Lysyl-bradykinin (10(-9)M) added to either the lumen or bath had no effect on base-line Lp. Collecting tubules which were exposed for 1 h to bath lysyl-bradykinin (10(-9)M) had a significantly diminished subsequent Lp in response to ADH (P less than 0.02). In tubules exposed to bath lysyl-bradykinin plus indomethacin (5 microM), the subsequent ADH response was normal. Lysyl-bradykinin (10(-9)M) added to the lumen had no effect on subsequent ADH response. We conclude that lysyl-bradykinin from the basolateral side inhibits the hydroosmotic response of the cortical collecting tubule to ADH, and that this inhibition is probably prostaglandin-mediated. Lysyl-bradykinin does not affect water flow from the luminal surface. These data indicate that the diuresis seen with kinin infusions may result, at least in part, from a direct epithelial effect. They also suggest a role of the renal kallikrein-kinin system in modulating water transport in vivo.
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PMID:Interactions of lysyl-bradykinin and antidiuretic hormone in the rabbit cortical collecting tubule. 642 78

Rat liver cells (the C-9 cell line) are capable of producing, from endogenously liberated arachidonic acid, prostaglandins I2, E2 and F2 alpha. Greater than 95% of these cyclooxygenase products is prostaglandin I2. Arachidonic acid metabolism is stimulated by treatment of the C-9 cells with epidermal growth factor, vasopressin, angiotensin II or thrombin. Stimulation by combined treatments with vasopressin, angiotensin II or thrombin is additive; but each stimulation, when incubated in the presence of epidermal growth factor, is synergistic. These stimulations are dependent on Ca++. They are inhibited by indomethacin and dexamethasone. The cells exhibit homologous, but not heterologous, desensitization to vasopressin and thrombin. The synergistic stimulation by epidermal growth factor and vasopressin is inhibited by prior treatment of the cells with epidermal growth factor.
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PMID:Arachidonic acid metabolism by rat liver cells (the C-9 cell line). 643 71

Prostaglandins are important modulators of the action of vasopressin. Others researchers have proposed that vasopressin stimulates prostaglandin synthesis, completing a negative feedback loop and thereby limiting vasopressin's antidiuretic effect. We have re-examined this question, using specific radioimmunoassay and thin-layer radiochromatography to determine prostaglandin synthesis by the toad bladder. Under control conditions, the bladder synthesizes prostaglandin (PG)E2 and thromboxane (TX)B2. There was no evidence for synthesis of PGE1 or PGF2 alpha by radioimmunoassay, or of other prostaglandins by radiochromatography. Furthermore, there was no evidence for metabolism of PGE2 by the bladder. Using a variety of protocols, in isolated epithelial cells as well as intact bladders, we were unable to detect any significant increase in PGE2 or TXB2 synthesis after stimulation with arginine vasopressin (AVP) or deamino-8-D-arginine vasopressin (DDAVP). Arachidonic acid, the specific precursor of prostaglandin synthesis, increased PGE2 synthesis twofold, and significantly inhibited AVP- and DDAVP-stimulated water flow by 60 and 75%, respectively. Naproxen and acetaminophen inhibited prostaglandin synthesis and enhanced water flow in response to AVP and DDAVP (44-54%). Our findings indicate that the toad bladder produces tow prostaglandins, PGE2 and TXB2, and that vasopressin does not alter their rate of synthesis. Because agents such as acetaminophen and naproxen inhibit prostaglandin synthesis and enhance vasopressin- and DDAVP-stimulated water flow, we suggest that it is the inhibitory effect of these agents on the hormone-independent rate of prostaglandin synthesis that is responsible for their enhancement of water flow. Furthermore, because AVP appears to increase prostaglandin synthesis by the intact kidney, we suggest that cells other than those of the collecting tubule are responsible for the increased prostaglandin production.
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PMID:Interaction of vasopressin and prostaglandins in the toad urinary bladder. 677 97

We investigated the regulation of cellular prostaglandin E2 (PGE2) biosynthesis in rabbit renomedullary interstitial cells in tissue culture. Arachidonic acid markedly stimulated PGE2 biosynthesis by these cells. Repeated exposure to arachidonic acid, resulted in progressively less stimulation of PGE2 biosynthesis. Potassium and dexamethasone diminished PGE2 biosynthesis by decreasing the rate of arachidonic acid release from the endogenous arachidonic acid storage pool. Hyperosmolality, like angiotensin II, bradykinin, and arginine vasopressin, stimulated PGE2 biosynthesis by increasing the rate of arachidonic acid release. Inhibitors of protein synthesis diminished angiotensin II-, bradykinin-, and arginine-vasopressin-stimulated PGE2 biosynthesis by decreasing hormone-stimulated arachidonic acid release. The effects of potassium, dexamethasone, arachidonic acid, and hyperosmolality on PGE2 biosynthesis were unaffected by protein synthesis inhibitors. Hormone-stimulated phospholipase activation is dependent on protein synthesis, whereas potassium, hyperosmolality, and dexamethasone alter the release of arachidonic acid from cellular lipids via a mechanism that is independent of protein synthesis.
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PMID:Regulation of prostaglandin E2 synthesis by angiotensin II, potassium, osmolality, and dexamethasone. 740 48


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