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)

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer surface of thymic epithelial cell plasma membrane from where OT is able to interact with neurohypophysial peptide receptors expressed by pre-T cells. Immature T cells bear a receptor of the V1 subtype, while OT receptors are predominantly expressed by cytotoxic CD8+ lymphocytes. In both T cell types, neurohypophysial peptide receptors transduce OT via the phosphoinositide pathway. Protein tyrosine phosphorylation is an early event of T cell activation. Western blots of murine pre-T cells (RL12-NP line) proteins probed with anti-phosphotyrosine (PY-20) revealed a great number of proteins the phosphorylation of which increased either with OT or vasopressin treatment. Two were immunoprecipitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were identified one as p125FAK and the other as a coprecipitating 130-kDa protein. The p125FAK is connected to the Ras/MAPK pathway and is also implicated in TCR/CD3 signalling in T cell. Another protein phosphorylated by OT in RL12-NP was identified as paxillin, a 68-kDa protein localised at focal adhesion sites and associated with p 125FAK. These results indicate that phosphorylation of focal adhesion kinase may be induced in pre-T cell by thymic OT.
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PMID:Neurohypophysial peptides stimulate the phosphorylation of pre-T cell focal adhesion kinases. 958 98

VP 4-8 as a highly potent behavioral-active metabolite of arginine-vasopressin (VP) has been studied in detail at four levels, i.e. ligand level, membrane binding level, intracellular level and nuclear level. The purpose of this chapter is to review and discuss the main results obtained from our recent pharmacological and biochemical investigations which are described as follows: 1, structure-function relationship of VP 4-8 and its analogs; 2, some characters of VP 4-8-specific binding, the distribution of the binding sites in the rat brain and the consequent effect on long-term potentiation of synaptic transmission; 3, a putative receptor-mediated signaling pathway involving second messenger IP3, immediately-early gene c-fos transcription and protein kinase PKC, CaMKII and MAPK; 4, peptide-induced enhancement of some crucial functional proteins such as calmodulin, nerve growth factor (NGF) and brain-derived nerve growth factor (BDNF). The physiological significance of the events following VP 4-8 administration and particularly, its possible role in learning and memory processes are discussed.
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PMID:Function and molecular basis of action of vasopressin 4-8 and its analogues in rat brain. 1007 88

The present study sought to determine the downstream consequences of V1a vasopressin receptor (V1aR) activation of Ca2+ signaling in cortical astrocytes. Results of these analyses demonstrated that V1aR activation led to a marked increase in both cytoplasmic and nuclear Ca2+. We also investigated V1aR activation of Ca2+-activated signaling kinases, protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and the mitogen-activated protein (MAP) kinases [MAPK and extracellular signal-regulated kinases 1 and 2 (ERK1/2)], their localization within cytoplasmic and nuclear compartments, and activation of their downstream nuclear target, the transcription factor cAMP response element-binding protein (CREB). Results of these analyses demonstrated that V1aR activation led to a significant rise in PKC, CaMKII, and ERK1/2 activation, with CaMKII and ERK1/2 demonstrating dynamic transport between cytoplasmic and nuclear compartments. Although no evidence of PKC translocation was apparent, PKC and CaMKs were required for activation and nuclear translocation of ERK1/2. Subsequent to CaMKII and ERK1/2 translocation to the nucleus, CREB activation occurred and was found to be dependent on upstream activation of ERK1/2 and CaMKs. These data provide the first systematic analysis of the V1aR-induced Ca2+ signaling cascade in cortical astrocytes. In addition, results of this study introduce a heretofore unknown effect of vasopressin, dynamic Ca2+ signaling between the cytoplasm and nucleus that leads to comparable dynamics of kinase activation and shuttling between cytoplasmic and nuclear compartments. Implications for development and regeneration induced by V1aR activation of CREB-regulated gene expression in cortical astrocytes are discussed.
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PMID:Vasopressin-induced cytoplasmic and nuclear calcium signaling in embryonic cortical astrocytes: dynamics of calcium and calcium-dependent kinase translocation. 1276 11

Vasopressin-activated Ca2+-mobilizing (VACM)-1 gene product is a 780-amino acid membrane protein that shares sequence homology with cullins, a family of genes involved in the regulation of cell cycle. However, when expressed in vitro, VACM-1 attenuates basal and vasopressin- and forskolin-induced cAMP production. Mutating the PKA-dependent phosphorylation site in the VACM-1 sequence (S730AVACM-1) prevents this inhibitory effect. To further examine the biological role of VACM-1, we studied the effect of VACM-1 and S730AVACM-1 proteins on cellular proliferation and gene expression in Chinese hamster ovary and COS-1 cells. Cellular proliferation of VACM-1-expressing cell lines was significantly lower compared with that of the vector-transfected cells, whereas it was significantly increased in S730AVACM-1-derived cell lines. Furthermore, expression of VACM-1 but not S730AVACM-1 protein retarded cytokinesis and prevented MAPK phosphorylation. Screening with the Human PathwayFinder-1 GEArray system and subsequent Western blot analysis demonstrated that VACM-1 induces p53 mRNA and protein expression. In summary, VACM-1 inhibits cellular growth by a mechanism that involves cAMP, MAPK phosphorylation, and p53 expression.
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PMID:VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways. 1291 6

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

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

Activation of V(1a) receptor triggers the expression of growth-related immediate-early genes (IEGs), including c-Fos and Egr-1. We found that pre-treatment of rat vascular smooth muscle A-10 cell line with the EGF receptor inhibitor AG1478 or the over-expression of an EGFR dominant negative mutant (HEBCD533) blocked the vasopressin-induced expression of IEGs, suggesting that activation of these early genes mediated by V(1a) receptor is via transactivation of the EGF receptor. Importantly, the inhibition of the metalloproteinases, which catalyzed the shedding of the EGF receptor agonist HB-EGF, selectively blocked the vasopressin-induced expression c-Fos. On the other hand, the inhibition of c-Src selectively blocked the vasopressin-induced expression of Egr-1. Interestingly, in contrast to the expression of c-Fos, the expression of Egr-1 was mediated via the Ras/MEK/MAPK-dependent signalling pathway. Vasopressin-triggered expression of both genes required the release of intracellular calcium, activation of PKC and beta-arrestin 2. These findings demonstrated that vasopressin up-regulated the expression of c-Fos and Erg-1 via transactivation of two distinct EGF receptor-dependent signalling pathways.
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PMID:Vasopressin up-regulates the expression of growth-related immediate-early genes via two distinct EGF receptor transactivation pathways. 1857 97

The unique phenotype of renal medullary cells allows them to survive and functionally adapt to changes of interstitial osmolality/tonicity. We investigated the effects of acute hypertonic challenge on AQP2 (aquaporin-2) water channel trafficking. In the absence of vasopressin, hypertonicity alone induced rapid (<10 min) plasma membrane accumulation of AQP2 in rat kidney collecting duct principal cells in situ, and in several kidney epithelial lines. Confocal microscopy revealed that AQP2 also accumulated in the trans-Golgi network (TGN) following hypertonic challenge. AQP2 mutants that mimic the Ser(256)-phosphorylated and -nonphosphorylated state accumulated at the cell surface and TGN, respectively. Hypertonicity did not induce a change in cytosolic cAMP concentration, but inhibition of either calmodulin or cAMP-dependent protein kinase A activity blunted the hypertonicity-induced increase of AQP2 cell surface expression. Hypertonicity increased p38, ERK1/2, and JNK MAPK activity. Inhibiting MAPK activity abolished hypertonicity-induced accumulation of AQP2 at the cell surface but did not affect either vasopressin-dependent AQP2 trafficking or hypertonicity-induced AQP2 accumulation in the TGN. Finally, increased AQP2 cell surface expression induced by hypertonicity largely resulted from a reduction in endocytosis but not from an increase in exocytosis. These data indicate that acute hypertonicity profoundly alters AQP2 trafficking and that hypertonicity-induced AQP2 accumulation at the cell surface depends on MAP kinase activity. This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity.
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PMID:Acute hypertonicity alters aquaporin-2 trafficking and induces a MAPK-dependent accumulation at the plasma membrane of renal epithelial cells. 1866 68

Prolactin (PRL) modulates maternal behavior and mediates hypothalamic pituitary adrenal axis inhibition during lactation via PRL receptors in the brain. To identify mechanisms mediating these effects, we examined the effects of PRL on signaling and CRH transcription in hypothalamic neurons in vivo and in vitro. Western blot of hypothalamic proteins from rats receiving intracerebroventricular PRL injection revealed increases in phosphorylation of the MAPK and ERK. Double-staining immunohistochemistry demonstrated phosphorylated ERK localization in parvocellular CRH neurons as well as magnocellular vasopressin and oxytocin neurons of the hypothalamic paraventricular (PVN) and supraoptic nuclei. PRL also induced ERK phosphorylation in vitro in the hypothalamic cell line, 4B, which expresses PRL receptors, and in primary hypothalamic neuronal cultures. Using reporter gene assays in 4B cells, or quantitative RT-PCR for primary transcript in hypothalamic cell cultures, PRL potentiated forskolin-stimulated CRH transcription through activation of the ERK/MAPK pathway. The effect of PRL in hypothalamic cell cultures was unaffected by tetrodotoxin, suggesting a direct effect on CRH neurons. The data show that PRL activates the ERK/MAPK pathway and facilitates CRH transcription in CRH neurons, suggesting that the inhibitory effect of PRL on hypothalamo-pituitary-adrenal axis activity reported in vivo is indirect and probably mediated through modulation of afferent pathways to the PVN. In addition, the prominent stimulatory action of PRL on the ERK/MAPK pathway in the hypothalamic PVN and supraoptic nucleus is likely to mediate neuroplasticity of the neuroendocrine system during lactation.
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PMID:Prolactin activates mitogen-activated protein kinase signaling and corticotropin releasing hormone transcription in rat hypothalamic neurons. 1902 92


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