UNIPROT:P01185 - FACTA Search

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)

Prostaglandins (PGs) are arachidonic acid (AA) derivatives via the PG endoperoxyde H synthase (PGHS) complex. Two PGHS isoforms have been recognized, constitutive (PGHS-1) and inducible (PGHS-2), respectively. Within the kidney, vascular endothelium mainly produces PGI2; the whole glomerulus synthesizes several prostanoids, the predominant AA metabolite in humans being PGI2; tubules and medullary interstitial cells produce mainly PGE2. Renal PGs modulates the action of other hormones and autacoids involved in the regulation of renal hemodynamics, glomerular filtration and the renal handling of sodium and water. Renal PGs are, at least in part, excreted into urine. Measurement of urinary PGs or their metabolites has been found to provide a reliable estimation of basal as well as stimulated PG synthesis. Patients with cirrhosis of the liver show an increased renal synthesis of vasodilating PGs, as indicated by the high urinary excretion of PGs and/or their metabolites. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to these patients causes a profound reduction in renal blood flow and glomerular filtration rate, a reduction in sodium excretion, and an impairment of free water clearance. These data clearly indicate that the increased renal synthesis of vasodilating PGs has a relevant role in maintaining renal hemodynamics, sodium and water excretion in a clinical setting characterized by a reduction of effective plasma volume and a striking activation of the major vasoconstricting systems, namely the renin-angiotensin-aldosterone, the sympathetic nervous system, and vasopressin. Patients with hepato-renal syndrome have a reduced renal synthesis of vasodilating PGE2 in the setting of a striking activation of endogenous vasoconstrictors and a maintained or increased renal production of thromboxane A2. Therefore, an imbalance between vasoconstricting systems and the renal vasodilator PGE2 was proposed to explain the renal failure observed in this condition. The urinary excretion of 2-3-dinor 6-keto-PGF1 alpha, an index of systemic PGI2 synthesis, is increased in patients with cirrhosis and hyperdynamic circulation, thus raising the possibility that systemic synthesis of PGI2 may contribute to the arterial vasodilatation of these patients. Finally, administration of exogenous prostanoids to patients with cirrhosis is not effective either in ameliorating renal function or in preventing the deleterious effect of NSAIDs.
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PMID:Arachidonic acid derivatives and renal function in liver cirrhosis. 935 64

Renal medullary prostaglandins are believed to exert an important functional role in antagonizing vasopressin effects in dehydration. Studies were undertaken to determine the effect of hyperosmolality on cyclooxygenase (COX) isoform expression in the renal medulla. COX-1 and COX-2 mRNA and protein levels were determined by RT-PCR or Western blotting in Sprague-Dawley rats on varying water intakes, in Brattleboro rats and in Long-Evans controls. Over a wide range of urinary tonicity, COX-2 expression correlated closely with urine osmolality levels (R = 0.872). COX-1 levels did not vary. Immunolocalization showed that the stimulation of COX-2 expression by dehydration occurred predominantly in the collecting duct. Hypertonicity caused by addition of NaCl produced a dose- and time-dependent stimulation of COX-2 expression in mIMCD-K2 cells as well as in MDCK cells. COX-1 was unaffected. In the same cell lines, mannitol, sucrose, and raffinose also had a stimulatory effect. The tonicity-stimulated COX-2 expression in mIMCD-K2 cells was almost completely blocked by a tyrosine kinase inhibitor, genistein at 100 microM. In MDCK cells transfected with a 2.7-kb COX-2 promoter and lacZ reporter construct, NaCl induced a twofold increase in beta-galactosidase activity. Using mIMCD-K2 cells, hypertonic NaCl (600 mosmol/kgH(2)O for 24 h) induced a 33-fold increase in PGE(2) release determined by enzyme immunoassay, an effect completely blocked by 3 microM indomethacin or the COX-2-specific blocker N-(2-cyclohexy-4-nitrophenyl)methanesulfonamide (NS-398). We conclude that in inner medulla, COX-2 but not COX-1 is upregulated by hyperosmolality.
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PMID:Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro. 1040 91

1. Selective inhibitors of cyclo-oxygenase-2 have been shown to be effective anti-inflammatory drugs with reduced gastrointestinal toxicity relative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, we examined the possibility that selective COX-2 inhibition, by blocking prostacyclin synthesis, would increase blood pressure and cause leukocyte adherence and platelet aggregation. 2. Normal rats and rats with hypertension induced by chronic administration of Nomega-nitro-L-arginine methylester were given celecoxib (10 mg kg(-1)) daily for 3 weeks. Celecoxib significantly elevated of blood pressure in both the normal and hypertensive rats (mean increase of >33 mm Hg after 3 weeks). 3. In normal rats, celecoxib had no effect on serum 6-keto prostaglandin (PG)F(1alpha) levels. Hypertensive rats exhibited a significant increase (82%) in serum 6-keto PGF(1alpha) levels, and this was reduced to the levels of normal rats by treatment with celecoxib. 4. Rats treated with celecoxib exhibited significant increases in weight gain (20%), plasma arginine-vasopressin levels (148%) and plasma urea (69%) relative to vehicle-treated controls. Plasma creatinine levels were unaffected by treatment with celecoxib, while plasma renin levels were significantly decreased (30%) relative to controls. 5. Superfusion of mesenteric venules with celecoxib (3 microM) in vivo resulted in significant increases in leukocyte adherence to the endothelium in both normal and hypertensive rats. 6. These studies suggest that suppression of COX-2 significantly influences vascular and/or renal function, leading to elevated blood pressure and leukocyte adherence.
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PMID:Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence. 1074 98

Bradykinin and a number of peptide hormones such as angiotensin, endothelin, and vasopressin stimulate anion secretion in rat epididymis via local formation of PGE(2). These effects are mediated by cyclooxygenase (COX)-1 isozyme. The present study was undertaken to assess the androgen control of COX expression in the epididymis. Adult male Sprague-Dawley rats were bilaterally castrated through a scrotal route. Reverse transcription-polymerase chain reaction was used to measure COX-1 and COX-2 mRNAs in the epididymis in normal and castrated rats. Anion secretion in epithelia grown from the epididymides of these rats was studied by the short-circuit current technique. In normal rats, COX-1 and COX-2 mRNAs were detected in the intact epididymis. Elimination of spermatozoa by the technique of efferent duct ligation or flushing out spermatozoa did not affect the expression of either enzyme in the epididymis, indicating that the epithelium, but not spermatozoa, expressed the enzymes. Castration caused a time-dependent decrease in expression of COX-1 and COX-2 mRNAs, which were partially restored upon testosterone replacement. In epithelia cultured from castrated rats, there was a complete loss of bradykinin-induced anion secretion. This effect was reversible upon testosterone replacement. Although epithelia from castrated rats did not respond to bradykinin, they could respond to cAMP, forskolin, and PGE(2) with only 20% loss of response magnitude when compared with epithelia from normal rats. These results suggest that the expression of COX-1 and COX-2 are dependent on androgen. The loss of COX-1 expression after castration correlates with the specific loss of anion secretion induced by bradykinin and possibly other hormones.
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PMID:Androgen control of cyclooxygenase expression in the rat epididymis. 1095 20

The kidney is the second most frequent target of serious adverse effects of non-steroidal antiinflammatory drugs (NSAIDs). The renal side effects of NSAIDs related to inhibition of cyclooxygenase (COX) comprise reduction in renal blood flow (RBF) and glomerular filtration rate (GFR), sodium/water retention, water intoxication and hyperkalemia. The discovery of two COX-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prosta noid production, led to the development of new NSAIDs: Preferential and specific COX-2 inhibitors, promising minimal NSAID-typical toxicity with equivalent efficacy. However, we learned that there is no clear distinction in "physiologic" constitutive COX-1 and "inflammatory" inducible COX-2. This is particular true for the kidney of humans and other mammalians, where COX-2 was found constitutively in meaningful amounts. Animal experiments and clinical trials with preferential and specific COX-2 inhibitors revealed that COX-2 is the critical enzyme for sodium excretion, renin release and likely antagonism of antidiuretic hormone. Additionally, a significant role of COX-2 for nephro genesis is suggested. For renal hemodynamics the given evidence point to COX-1 as the predominant enzyme, but further investigations are required. In summary, the gain of renal safety by use of preferential or specific COX-2 inhibitors is small or negligible with respect to sodium retention, hyperkalemia and probably water intoxication. These drugs may be advantageous regarding renal perfusion, but presently the same precautions as for conventional NSAIDs must be used.
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PMID:COX-2 and the kidneys. 1110 61

The aim of the present study was to determine the effect of social stress and significance of prostaglandins (PG) generated by constitutive and inducible cyclooxygenase (COX-1 and COX-2) in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by corticotropin releasing hormone (CRH) under basal and social crowding stress conditions. The stressed rats were crowded in groups of 24 to a cage for 3 or 7 days, whereas the control animals were haused in groups of 7 to a cage of the same size. The activity of HPA axis was determined by measuring plasma ACTH and serum corticosterone levels 1 h after i.p. CRH administration. Inhibitors of COX-1, piroxicam (0.2, 2.0, and 5.0 mg/kg), and COX-2, compound NS-398 (0.2 and 2.0 mg/kg), were administered i.p. 15 min prior to CRH (0.1 microg/kg i.p.) to control or crowded rats. The obtained results indicate that social stress for 3 and 7 days markedly intensifies the stimulatory action of CRH on ACTH secretion. Neither piroxicam nor NS-398 induce any significant effect on the CRH-elicited ACTH and corticosterone secretion in non-stressed or crowded rats. Therefore, PG generated by COX-1 or COX-2 do not participate to a significant extent in the stimulation of HPA axis by CRH under either basal conditions or during crowding stress. These results also indicate that the stimulatory action of CRH on ACTH secretion is not only completely resistant to desensitization but is sensitized during social crowding stress. The results contrast with a significant involvement of PG in the vasopressin-induced stimulation of HPA response during crowding stress.
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PMID:Effect of cyclooxygenase inhibitors on the CRH-induced pituitary-adrenocortical activity during crowding stress. 1267 22

The antagonism between prostaglandin and vasopressin represents a classic negative feedback loop. It is not clear whether cyclooxygenase (COX)-2 and/or COX-1 expression is involved in elevated prostaglandin production stimulated by vasopressin in vivo. In the present study, we explored vasopressin regulation of medullary COX-2 and COX-1 expression acutely and chronically in rats. Medullary COX-1 expression was moderately lower and COX-2 expression was significantly lower in adult male Brattleboro rats than age-matched Long-Evans controls. Chronic treatment of Brattleboro rats with vasopressin for 1 wk led to a decrease in urine volume and a moderate increase in medullary COX-1; in contrast, medullary COX-2 expression was almost undetectable in untreated rats but was dramatically up-regulated with vasopressin treatment and was accompanied by increased urinary prostaglandin E(2) excretion. Further investigation revealed that both V1 and V2 receptors were involved in chronic medullary COX-1 and COX-2 up-regulation. Acute treatment with specific V1 or V2 receptor agonists resulted in specific increases in medullary COX-2, which was prevented by furosemide. Vasopressin did not affect COX-2 expression in cultured renomedullary interstitial cells. These data demonstrate that vasopressin stimulates medullary COX-2 expression through activation of both V1 and V2 receptors, and this stimulation is indirect and probably involves increased medullary electrolyte tonicity.
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PMID:Regulation of cyclooxygenase expression by vasopressin in rat renal medulla. 1468 11

Mesangial cells play an important role in glomerular function. They are an important source of cyclooxygenase (COX)-derived arachidonic acid metabolites, including prostaglandin E(2) and prostacyclin. Prostacyclin receptor (IP) mRNA was amplified from cultured mesangial cell total RNA by RT-PCR. While the prostaglandin E(2) receptor subtype EP(2) was not detected, EP(1,3,4) mRNA was amplified. Also, IP protein was noted in mesangial cells, proximal tubules, inner medullary collecting ducts, and the inner and outer medulla. But no protein was detected in whole cortex preparations. Prostacyclin analogues: cicaprost and iloprost, increased cAMP levels in mesangial cells. On the other hand, arginine-vasopressin and angiotensin II increased intracellular calcium in mesangial cells, but cicaprost, iloprost and prostaglandin E(2) had no effect. Moreover, a 50% inhibition of cicaprost- and iloprost-cAMP stimulation was observed upon mesangial cell exposure to 25 and 35 mM glucose for 5 days. But no change in IP mRNA was observed at any glucose concentration or time exposure. Although 25 mM glucose had no effect on COX-1 protein levels, COX-2 was increased up to 50%. In contrast, PGIS levels were reduced by 50%. Thus, we conclude that the prostacyclin/IP system is present in cultured rat mesangial cells, coupling to a cAMP stimulatory pathway. High glucose altered both enzymes in the PGI(2) synthesis pathway, increasing COX-2 but reducing PGIS. In addition, glucose diminished the cAMP response to prostacyclin analogues. Therefore, glucose attenuates the PGI(2)/IP system in cultured rat mesangial cells.
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PMID:Characterization of the PGI2/IP system in cultured rat mesangial cells. 1506 48

The review presents our results on the regulatory role of prostaglandins (PG) and nitric oxide (NO) in the activation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic, adrenergic and histaminergic systems and by neurohormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) under basal conditions. The synthesis of endogenous PG or NO was inhibited by non-selective and selective cyclooxygenase (COX) antagonists and nitric oxide synthase (NOS) blockers given 15 min before the respective receptor agonist and HPA axis activity was assessed 1 h later by measuring plasma ACTH and serum corticosterone levels. The muscarinic agent - carbachol-induced HPA response was considerably supressed by piroxicam, a predominantly constitutive cyclooxygenase (COX-1) inhibitor and significantly diminished by indomethacin, a non-selective COX blocker, but was unaffected by compound NS-398, an inducible cyclooxygenase (COX-2) antagonist. A non-selective NOS antagonist L-NAME and neuronal NOS blocker L-NNA significantly intensified the carbachol-induced corticosterone secretion. The nicotine-induced increase in ACTH and corticosterone response was significantly supressed by piroxicam, and diminished by indomethacin, but was significantly augmented by L-NAME and L-NNA. The inhibition of PG synthesis by indomethacin totally abolished or reversed the increase of nicotine-induced hormone responses to both NOS blockers. The i.c.v. phenylephrine, an alpha(1)-adrenergic receptor agonist - evoked HPA response was significantly impaired by piroxicam and compound NS-398 and more potently reduced by L-NAME. The i.c.v. clonidine, an alpha(2)-adrenergic agonist - elicited HPA response was also considerably decreased by piroxicam, compound NS-398 and L-NAME. By contrast, the stimulatory effect of i.c.v. isoprenaline, a non-selective beta-adrenergic agonist, was not altered by either COX or NOS inhibitors. The i.c.v. histamine- and HTMT, a histamine H(1)-agonist-induced ACTH and corticosterone response were significantly diminished by piroxicam and indomethacin, respectively. Compound NS-398, did not markedly alter the HPA response to HTMT or amthamine, a histamine H(2) receptor agonist. Inhibition of endogenous NO synthesis by a neuronal NOS inhibitor 7-nitroindazole markedly enhanced the histamine-induced hormone secretion, abolished the HTMT-induced response and did not substantially alter the amthamine-evoked ACTH and corticosterone secretion. COX blockers did not significantly affect the CRH-induced HPA response and the inhibition of NO synthesis by L-NNA markedly intensified ACTH response. The vasopressin-stimulated increase in HPA response, was considerably reduced by the inhibition of PG synthesis by both COX antagonists while inhibition of NO synthesis by NOS blockers greatly enhanced this response. The involvement of PG and NO in the neurohormonal regulation of HPA activity depends mainly on greatly complex and tightly regulated mechanisms at the level of second messengers IP(3) and adenylyl cyclase systems.
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PMID:Nitric oxide and prostaglandin systems in the stimulation of hypothalamic-pituitary-adrenal axis by neurotransmitters and neurohormones. 1561 36

Prostaglandins have an important role in renal salt and water reabsorption. PGE2 is the main kidney prostaglandin and is thought to be mainly produced in the kidney inner medulla (IM). There are indications that PGE2 synthesis in nephrogenic (NDI) and central (CDI) diabetes insipidus is altered. We hypothesize that the expression of the major PGE2 synthesis enzymes cyclooxygenases 1 and 2 (COX-1, COX-2) and membrane-associated PGE2 synthase (mPGES) is altered in the kidneys of rats with NDI and CDI. Wistar rats treated with lithium for 4 wk were used as the NDI model. One-half of the NDI model rats were additionally dehydrated for 48 h. Brattleboro (BB) rats that lack endogenous antidiuretic hormone were used as the CDI model. Expression and localization of COX-1, COX-2, and mPGES in IM, inner stripe of outer medulla (ISOM), and cortex were determined by immunoblotting and immunohistochemistry. In lithium-induced NDI, expression of COX-1, COX-2, and mPGES was markedly decreased in IM. In ISOM and cortex, COX-1 expression was marginally reduced and mPGES expression was unaltered. COX-2 expression was undetected in ISOM and marginally increased in cortex. Consistent with this, the density of COX-2-expressing cells in macula densa was significantly increased, indicating differential regulation of COX-2 in IM and cortex. Dehydration of NDI rats resulted in a marked increase in COX-2 immunolabeling in IM interstitial cells, and there was no significant change in COX-1 and mPGES expression in any kidney zone. Treatment of DDAVP in BB rats for 6 days resulted in a markedly increased expression of COX-1, COX-2, and mPGES in IM. In the cortex, there were no changes in the expression of COX-1 and mPGES, whereas COX-2 expression was decreased. These results identify markedly reduced expression of COX-1, COX-2, and mPGES in IM in lithium-induced NDI. Furthermore, there were major changes in the expression of COX-1, COX-2, and mPGES in rats with CDI.
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PMID:Altered expression of COX-1, COX-2, and mPGES in rats with nephrogenic and central diabetes insipidus. 1564 90

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