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)

JAK (Janus-activated kinase)-STAT (signal transducers and activators of transcription) signaling is a major signal transduction pathway in mammalian cells. Different growth factors and cytokines were reported as activators of the JAK-STAT pathway in various cell types. Interestingly, arginine-vasopressin (AVP) was never reported as an inducer of the JAK-STAT pathway. In the present study, we show for the first time that AVP stimulation of vascular smooth muscle cells (VSMCs) induces STAT3 tyrosine and serine phosphorylation, followed by nuclear translocation of the phosphorylated STAT3. In addition, we found that AVP induced JAK2 tyrosine phosphorylation. Taken together, these results demonstrate that AVP activates the JAK-STAT pathway in VSMCs. Furthermore, our results indicate that AVP-induced STAT3 tyrosine phosphorylation requires both JAK2 and c-Src tyrosine kinases. The present study also implicates that extracellular signal-regulated kinase (ERK1/2), which are serine/threonine kinases, are the mediators of STAT3 serine phosphorylation upon AVP stimulation. We further suggest that AVP-induced STAT3 serine phosphorylation negatively modulates AVP-induced STAT3 tyrosine phosphorylation. Finally, our results implicate a novel role for the JAK-STAT pathway, mediating AVP-induced VSMC hypertrophy.
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PMID:Arginine-vasopressin activates the JAK-STAT pathway in vascular smooth muscle cells. 1656 10

We have sequenced a 4.9kb clone (KLB22) which shares 99% sequence homology with the rabbit vasopressin-activated calcium mobilizing (VACM-1) protein. The 5' terminus sequence of KLB22 cDNA (nucleotides 1-1961) is continuous and overlapping with nucleotides 1226-3186 of the VACM-1 cDNA sequence. The 3'UTR of KLB22 cDNA extends beyond the 3'UTR of VACM-1 by 2999nt. KLB22 cDNA encodes a 497 amino acid protein, which putatively begins at Met 284 of the 780 amino acid VACM-1 protein. The in vitro translation of KLB22 cDNA yields a 59kDa protein. When expressed in cos-1 cells, the truncated VACM-1 protein localizes to the nucleus. KLB22 cDNA transfected cells show increased growth rates and increased levels of phosphorylated MAPK when compared to the vector or to VACM-1 cDNA transfected cells. Finally, in vivo, KLB22 protein expression is tissue specific and can be detected in kidney and in heart atrium. These results suggest that truncated VACM-1 cDNA (KLB22) increases cell proliferation through a MAPK pathway.
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PMID:Truncated form of VACM-1/cul-5 with an extended 3' untranslated region stimulates cell growth via a MAPK-dependent pathway. 1658 Oct 22

Previous studies show that binding of nuclear proteins to GAGA repeats (GAGA box) in the vasopressin type 1b receptor (V1bR) promoter is essential for transcriptional initiation of the gene. To determine whether increased vasopressin (VP) during stress activates V1bR expression through the GAGA box, we examined the effects of VP on GAGA binding activity and on the ability of the V1bR promoter to recruit RNA polymerase in the hypothalamic cell line, H32. In chromatin immunoprecipitation assays, VP induced RNA polymerase II recruitment by the wild type V1bR promoter but not by a construct with the major GAGA box deletion. VP (10 min) also increased binding of nuclear proteins to radiolabeled GAGA oligonucleotides in electromobility shift assays. VP-induced GAGA binding activity was potentiated by the protein kinase C inhibitor, calphostin C, and was prevented by the MEK inhibitor, UO126, and the epidermal growth factor receptor (EGFR) inhibitor, AG1478, suggesting that VP activates GAGA binding through transactivation of the EGFR. This was confirmed by western blot experiments showing rapid increases in phospho ERK after incubation with VP, an effect that was potentiated by calphostin C and inhibited by UO12 and AG1478, as well as by the ability of VP to phosphorylate the EGFR. Using receptor selective VP analogs we showed that both V1aR and V1bR subtypes can mediate GAGA binding activation in H32 cells. This study demonstrates that VP stimulates GAGA binding to the V1bR promoter through transactivation of the EGFR and MAP kinase. The data support the hypothesis that VP contributes to pituitary V1bR upregulation during stress through GAGA binding-mediated transcriptional activation.
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PMID:Vasopressin increases GAGA binding activity to the V1b receptor promoter through transactivation of the MAP kinase pathway. 1672 Jul 25

The V2 vasopressin receptor (V2R) activates the mitogen activated protein kinases (MAPK) ERK1/2 through a mechanism involving the scaffolding protein beta arrestin. Here we report that this activating pathway is independent of G alpha s, G alpha i, G alpha q or G betagamma and that the V2R-mediated activation of G alpha s inhibits ERK1/2 activity in a cAMP/PKA-dependent manner. In the HEK293 cells studied, the beta arrestin-promoted activation was found to dominate over the PKA-mediated inhibition of the pathway, leading to a strong vasopressin-stimulated ERK1/2 activation. Despite the strong MAPK activation and in contrast with other GPCR, V2R did not induce any significant increase in DNA synthesis, consistent with the notion that the stable interaction between V2R and beta arrestin prevents signal propagation to the nucleus. Beta arrestin was found to be essential for the ERK1/2 activation, indicating that the recruitment of the scaffolding protein is necessary and sufficient to initiate the signal in the absence of any other stimulatory cues. Based on the use of selective pharmacological inhibitors, dominant negative mutants and siRNA, we conclude that the beta arrestin-dependent activation of ERK1/2 by the V2R involves c-Src and a metalloproteinase-dependent trans-activation event. These findings demonstrate that beta arrestin is a genuine signalling initiator that can, on its own, engage a MAPK activation machinery upon stimulation of a GPCR by its natural ligand.
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PMID:The V2 vasopressin receptor stimulates ERK1/2 activity independently of heterotrimeric G protein signalling. 1685 42

The fine control of NaCl absorption regulated by hormones takes place in the distal nephron of the kidney. In collecting duct principal cells, the epithelial sodium channel (ENaC) mediates the apical entry of Na(+), which is extruded by the basolateral Na(+),K(+)-ATPase. Simian virus 40-transformed and "transimmortalized" collecting duct cell lines, derived from transgenic mice carrying a constitutive, conditionally, or tissue-specific promoter-regulated large T antigen, have been proven to be valuable tools for studying the mechanisms controlling the cell surface expression and trafficking of ENaC and Na(+),K(+)-ATPase. These cell lines have made it possible to identify sets of aldosterone- and vasopressin-stimulated proteins, and have provided new insights into the concerted mechanism of action of serum- and glucocorticoid-inducible kinase 1 (Sgk1), ubiquitin ligase Nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2), and 14-3-3 regulatory proteins in modulating ENaC-mediated Na(+) currents. Epidermal growth factor and induced leucine zipper protein have also been shown to repress and stimulate ENaC-dependent Na(+) absorption, respectively, by activating or repressing the mitogen-activated protein kinase externally regulated kinase(1/2). Overall, these findings have provided evidence suggesting that multiple pathways are involved in regulating NaCl absorption in the distal nephron.
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PMID:Regulation of NaCl transport in the renal collecting duct: lessons from cultured cells. 1693 17

Extracellular regulated kinase (ERK) signalling is believed to play roles in various aspects of circadian clock mechanisms. In this study, we show in rat that the nuclear versus cytoplasmic intracellular distribution of the phosphorylated forms of ERK1/2 (P-ERK1/2) in the central clock, namely the suprachiasmatic nucleus (SCN), is proportionally constant across the light/dark cycle while the spatial distribution and neurochemical phenotype of cells expressing these activated forms are time-regulated according to a daily rhythm and light-regulated. P-ERK1/2 was exclusively found in neuronal elements. At daytime, it was detected throughout the dorsoventral extent of the SCN, partly within neurons synthesizing either arginine-vasopressin or vasoactive intestinal peptide (VIP). At night time, it was segregated in the ventrolateral aspect of the nucleus, within a cluster of cells 45% of which were gastrin-releasing peptide (GRP) neurons with or without co-localization with VIP. After a light pulse at night, expression of P-ERK1/2 increased in GRP neurons but also appeared in a population of neurons that stained for VIP only. These data show that the GRP neurons are closely associated with ERK1/2 activation at night and point to the importance of ERK1/2 signalling not only in intra-SCN transmission of photic information but also in maintenance of neuronal rhythms in the SCN.
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PMID:Nocturnal expression of phosphorylated-ERK1/2 in gastrin-releasing peptide neurons of the rat suprachiasmatic nucleus. 1725 Jun 49

[Arg8]-vasopressin (AVP) is an essential hormone for maintaining osmotic homeostasis and is known to be a potent vasoconstrictor that regulates the cardiovascular system. In the present study, cardiomyocytes were isolated from neonatal mice and used to investigate the effects of AVP on cardiac hypertrophy. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that vasopressin V1A receptor mRNA, but not V1B or V2 receptor mRNA, was expressed in primary cultured neonatal mouse cardiomyocytes. By exposing the cultured neonatal cardiomyocytes to AVP for 24 h, cell surface areas were significantly increased, suggesting that AVP could induce cardiomyocyte growth. We then investigated the expression level of the atrial natriuretic peptide (ANP), which is a marker of cardiac hypertrophy. Stimulation with AVP increased the expression of cardiomyocyte ANP mRNA in a dose- and time-dependent manner. Immunocytochemical studies showed that stimulation with AVP significantly increased the expression of the ANP protein as well. Furthermore, AVP administration activated extracellular signal-regulated kinase (ERK)1/2 in cardiomyocytes. The effects of AVP on these parameters were significantly inhibited by a selective vasopressin V1A receptor antagonist, OPC-21268, and were not observed in cardiomyocytes from mice lacking the vasopressin V1A receptor. In vivo cardiac hypertrophy in response to pressure overload was attenuated in vasopressin V1A receptor-deficient (V1AR-KO) mice. Taken together, our data suggest that AVP promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor, which is in part regulated by the pathway of ERK1/2 signaling.
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PMID:Vasopressin promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor in neonatal mice. 1727 6

Recently, we synthesized and characterized the first selective V(1b) vasopressin (VP)/oxytocin receptor agonist, d[Cha(4)]arginine vasopressin. However, this agonist was only selective for the human receptors. We thus decided to design a selective V(1b) agonist for the rodent species. We started from previous observations showing that modifying [deamino(1),Arg(8)]VP in positions 4 and 8 altered the rat VP/oxytocin receptor selectivity. We synthesized a series of 13 [deamino(1),Arg(8)]VP analogs modified in positions 4 and 8. Among them, one seemed very promising, d[Leu(4), Lys(8)]VP. In this paper, we describe its pharmacological and physiological properties. This analog exhibited a nanomolar affinity for the rat, human, and mouse V(1b) VP receptors and a strong V(1b) selectivity for the rat species. On AtT20 cells stably transfected with the rat V(1b) receptor, d[Leu(4), Lys(8)]VP behaved as a full agonist on both phospholipase C and MAPK assays. Additional experiments revealed its ability to induce the internalization of enhanced green fluorescent protein-tagged human and mouse V(1b) receptors as expected for a full agonist. Additional physiological experiments were performed to further confirm the selectivity of this peptide. Its antidiuretic, vasopressor, and in vitro oxytocic activities were weak compared with those of VP. In contrast, used at low doses, its efficiency to stimulate adrenocorticotropin or insulin release from mouse pituitary or perfused rat pancreas, respectively, was similar to that obtained with VP. In conclusion, d[Leu(4), Lys(8)]VP is the first selective agonist available for the rat V(1b) VP receptor. It will allow a better understanding of V(1b) receptor-mediated effects in rodents.
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PMID:Pharmacological and physiological characterization of d[Leu4, Lys8]vasopressin, the first V1b-selective agonist for rat vasopressin/oxytocin receptors. 1749 6

Bone loss resulting from chronic ethanol (EtOH) abuse is frequently accompanied by altered vitamin D3 homeostasis. In the current study, we examined EtOH effects in a female rat model in which control or EtOH-containing diets were infused intragastrically. EtOH treatment reduced plasma 1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) coincident with a decrease in renal CYP27B1 (25(OH)D3 1alpha-hydroxylase) mRNA and an increase in expression of renal CYP24A1 (1,25 (OH)2 D3- 24-hydroxylase). EtOH induction of CYP24A1 occurred as a result of increased transcription and was also observed in vitro in primary cultures of rat renal proximal tubule cells (RPTCs) and in NRK-52E cells. Synergistic induction of CYP24A1 by EtOH in combination with 1,25 (OH)2 D3 was observed. The major EtOH metabolizing enzymes, alcohol dehydrogenase-1 and CYP2E1, were induced by EtOH in RPTCs. Inhibition of EtOH metabolism by 4-methylpyrazole inhibited the induction of CYP24A1 mRNA. CYP24A1 mRNA induction in RPTCs was also inhibited by the protein synthesis inhibitor cycloheximide. CYP24A1 was also induced after hydrogen peroxide treatment, and EtOH treatment of RPTCs resulted in production of reactive oxygen species as measured by flow cytometry using the fluorescent probe dichlorofluorescin acetate. In addition, inhibition of MAPK signaling pathways with the MAPK kinase inhibitor U0126 or the p38 inhibitor SB203580 inhibited EtOH induction of CYP24A1. Our data suggest that EtOH reduces circulating 1,25 (OH)2 D3 concentrations as the result of CYP24A1 induction that is mediated via MAPK activation resulting from renal oxidative stress produced by local metabolism of EtOH via CYP2E1 and antidiuretic hormone-1.
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PMID:Chronic ethanol consumption leads to disruption of vitamin D3 homeostasis associated with induction of renal 1,25 dihydroxyvitamin D3-24-hydroxylase (CYP24A1). 1816 28

The neuropeptide oxytocin (OT) modulates social behaviours and is an important anxiolytic substance of the brain. However, sites of action and the intracellular signalling pathways downstream of OT receptors (OTR) within the brain remain largely unknown. In the present studies, we localized the anxiolytic effect of OT by bilateral microinfusion of OT (0.01 nmol/0.5 microL) into the hypothalamic paraventricular nucleus (PVN) in male rats using both the elevated plus-maze and the light-dark box. Moreover, intracerebroventricular administration of OT, but not of the related neuropeptide vasopressin (VP), dose-dependently activated the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade. Specifically, OT induced the phosphorylation of Raf-1, MEK1/2 and ERK1/2 in the hypothalamus in vivo and in hypothalamic H32 neurons via EGF receptors. OT-induced ERK1/2 phosphorylation was immunohistochemically localized within VP neurons of the PVN and the supraoptic nucleus. Importantly, the anxiolytic effect of OT within the PVN was prevented by local inhibition of the MAP kinase cascade with a MEK1/2 inhibitor (U0126, 0.5 nmol/0.5 microL) locally infused prior to OT, indicating the causal involvement of this intracellular signalling cascade in the behavioural effect of OT. OT effects within the hypothalamus may have far-reaching implications for the regulation of emotionality and social behaviours and, consequently, for the development of possible therapeutic strategies to treat affective disorders. Thus, OTR agonism or activation of the ERK1/2 cascade, specifically within the hypothalamus, may provide therapeutically relevant mechanisms.
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PMID:Oxytocin reduces anxiety via ERK1/2 activation: local effect within the rat hypothalamic paraventricular nucleus. 1841 15


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