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)

In GN4 rat liver epithelial cells, angiotensin II (Ang II) and other agonists which activate phospholipase C stimulate tyrosine kinase activity in a calcium-dependent, protein kinase C (PKC)-independent manner. Since Ang II also produces a proliferative response in these cells, we investigated downstream signaling elements traditionally linked to growth control by tyrosine kinases. First, Ang II, like epidermal growth factor (EGF), stimulated AP-1 binding activity in a PKC-independent manner. Because increases in AP-1 can reflect induction of c-Jun and c-Fos, we examined the activity of the mitogen-activated protein (MAP) kinase family members Erk-1 and -2 and the c-Jun N-terminal kinase (JNK), which are known to influence c-Jun and c-Fos transcription. Ang II stimulated MAP kinase (MAPK) activity but only approximately 50% as effectively as EGF; again, these effects were independent of PKC. Ang II also produced a 50- to 200-fold activation of JNK in a PKC-independent manner. Unlike its smaller effect on MAPK, Ang II was approximately four- to sixfold more potent in activating JNK than EGF was. Although others had reported a lack of calcium ionophore-stimulated JNK activity in lymphocytes and several other cell lines, we examined the role of calcium in GN4 cells. The following results suggest that JNK activation in rat liver epithelial cells is at least partially Ca(2+) dependent: (i) norepinephrine and vasopressin hormones that increase inositol 1,4,5-triphosphate stimulated JNK; (ii) both thapsigargin, a compound that produces an intracellular Ca(2+) signal, and Ca(2+) ionophores stimulated a dramatic increase in JNK activity (up to 200-fold); (iii) extracellular Ca(2+) chelation with ethylene glycol tetraacetic acid (EGTA) inhibited JNK activation by ionophore and intracellular chelation with 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl-ester (BAPTA-AM) partially inhibited JNK activation by Ang II or thapsigargin; and (iv) JNK activation by Ang II was inhibited by pretreatment of cells with thapsigargin and EGTA, a procedure which depletes intracellular Ca(2+) stores. JNK activation following Ang II stimulation did not involve calmodulin; either W-7 nor calmidizolium, in concentrations sufficient to inhibit Ca(2+)/calmodulin-dependent kinase II, blocked JNK activation by Ang II. In contrast, genistein, in concentrations sufficient to inhibit Ca(2+)-dependent tyrosine phosphorylation, prevented Ang II and thapsigargin-induced JNK activation. In summary, in GN4 rat liver epithelial cells, Ang II stimulates JNK via a novel Ca(2+)-dependent pathway. The inhibition by genistein suggest that Ca(2+)-dependent tyrosine phosphorylation may modulate the JNK pathway in a cell type-specific manner, particularly in cells with a readily detectable Ca(2+)-regulated tyrosine kinase.
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PMID:Angiotensin II stimulates calcium-dependent activation of c-Jun N-terminal kinase. 756 68

Activation of mitogen-activated protein kinases (MAPKs) was examined in the A7r5 rat vascular smooth muscle cell line. Treatment of A7r5 cells with vasopressin, phorbol ester (PMA), or serum resulted in activation of two MAPKs, Erk-1 and Erk-2. Phosphatidylinositol-specific phospholipase C was activated in response to vasopressin but not to PMA. Vasopressin and PMA both caused maximal activation of PLD within 5 minutes. Application of bacterial phospholipase D (PLD) to A7r5 cells increased phosphatidic acid to levels similar to those seen with vasopressin or PMA. Acute exposure of the cells to vasopressin, PMA, or PLD increased phosphorylation of many of the same cytosolic and membrane proteins. However, bacterial PLD did not promote significant activation of Erk-1 and Erk-2. Phosphatidic acid and lysophosphatidic acid (LPA) likewise did not stimulate MAPK activity in A7r5 cells. Serum and vasopressin stimulated DNA synthesis when present for more than 30 min, while PLD, PMA, phosphatidic acid, and LPA were not mitogenic. These data suggest that activations of MAPKs and PLD are concurrent but independent responses to vasopressin in A7r5 cells. Acute activation of these enzymes is not sufficient to simulate DNA synthesis.
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PMID:Activations of mitogen-activated protein kinases and phospholipase D in A7r5 vascular smooth muscle cells. 808 51

The novel substance P (SP) analogue, [D-Arg1,D-Trp5,7,9,Leu11]SP like [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP inhibited DNA synthesis induced by bombesin, vasopressin, and bradykinin, but did not interfere with the mitogenic response induced by other growth factors or pharmacological agents in Swiss 3T3 cells. [D-Arg1,D-Trp5, 7,9,Leu11]SP reversibly inhibited bombesin-induced DNA synthesis, causing a 6-fold greater rightward shift in the bombesin dose response than [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP at identical concentrations (10 microM). We found that the new, more potent, SP analogue coordinately and reversibly inhibited bombesin-induced Ca2+ mobilization and protein kinase C (PKC) and mitogen-activated protein (MAP) kinase activation. The dose-response curves for bombesin-induced Ca2+ mobilization and MAP kinase activation were similarly displaced (51- and 40-fold, respectively) by [D-Arg1, D-Trp5,7,9,Leu11]SP. In addition, [D-Arg1,D-Trp5,7,9,Leu11]SP reversibly inhibited bombesin-induced tyrosine phosphorylation of Mr 110,000-130,000 and 70,000-80,000 bands as well as p125 focal adhesion kinase. [D-Arg1,D-Trp5,7,9,Leu11]SP also reversibly and coordinately inhibited vasopressin-induced Ca2+ mobilization, PKC stimulation, MAP kinase activation, tyrosine phosphorylation, and DNA synthesis in Swiss 3T3 cells. Surprisingly, deletion of the terminal Leu of [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP to yield [D-Arg1, D-Phe5,D-Trp7,9]SP1-10 resulted in a selective loss of inhibitory activity of this analogue against bombesin- but not vasopressin-stimulated DNA synthesis, Ca2+ mobilization, and MAP kinase activation. Collectively, these results suggest that SP analogues act at the receptor level to coordinately and reversibly antagonize bombesin- or vasopressin-induced signal transduction in Swiss 3T3 cells.
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PMID:[D-Arg1,D-Trp5,7,9,Leu11]Substance P coordinately and reversibly inhibits bombesin- and vasopressin-induced signal transduction pathways in Swiss 3T3 cells. 891 Jun 12

Recently, we demonstrated that elevated blood pressure activates mitogen-activated protein (MAP) kinases in rat aorta. Here we provide evidence that the vascular response to acute hypertension also includes induction of MAP kinase phosphatase-1 (MKP-1), which has been shown to function in the dephosphorylation and inactivation of MAP kinases. Restraint or immobilization stress, which leads to a rapid rise in blood pressure, resulted in a rapid and transient induction of MKP-1 mRNA followed by elevated MKP-1 protein expression in rat aorta. That the induction of MKP-1 by restraint was due to the rise in blood pressure was supported by the finding that several different hypertensive agents (phenylephrine, vasopressin, and angiotensin II) were likewise capable of eliciting the response, and sodium nitroprusside, a nonspecific vasodilator agent that prevented the acute rise in blood pressure in response to the hypertensive agents, abrogated MKP-1 mRNA induction. The in vivo effects could not be mimicked by treatment of cultured aortic smooth muscle cells with similar doses of the hypertensive agents. These findings support a role for MKP-1 in the in vivo regulation of MAP kinase activity during hemodynamic stress.
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PMID:Induction of mitogen-activated protein kinase phosphatase-1 during acute hypertension. 923 29

The vasopressin (AVP) V3 pituitary receptor (V3R) is a G protein-coupled corticotropic phenotypic marker that is overexpressed in ACTH-hypersecreting tumors. Studies of the agonist/antagonist binding profile and signal transduction pathways linked to the human V3R have been limited because of the scarcity of this protein. To define the signals activated by V3Rs and the eventual changes triggered by developmental or pathological receptor regulation, we developed Chinese hamster ovary (CHO)-V3 cells stably expressing low, medium, or high levels of human V3Rs (binding capacity, <10, 10-25, and 25-100 pmol/mg, respectively). The affinity of the V3R for 21 peptide and nonpeptide AVP analogs was clearly distinct from that exhibited by the human V1R and V2R. AVP triggered stimulation of phospholipase C in CHO-V3 cells (partially sensitive to treatment with pertussis toxin) with a potency directly proportional to receptor density. V3R-mediated arachidonic acid release also was also sensitive to pertussis toxin and more efficacious in cells exhibiting medium than in those with high receptor density. AVP also stimulated the pertussis toxin-insensitive uptake of [3H]thymidine in CHO-V3 cells. The concentration-response curves for this effect were monophasic in cells expressing low and medium levels of V3Rs; on the contrary, a biphasic curve was observed in cells with high V3R density. Coupling of V3R to increased production of cAMP was only observed in CHOV3 high cells, suggesting a negative relationship between increased cAMP production and DNA synthesis. Activation of mitogen-activated protein kinases by V3R was pertussis toxin insensitive, but was dependent on activation of phospholipase C and protein kinase C; both the level and duration of activation were a function of the receptor density. Thus, the human V3R has a pharmacological profile clearly distinct from that of the human V1R and V2R and activates several signaling pathways via different G proteins, depending on the level of receptor expression. The increased synthesis of DNA and cAMP levels observed in cells expressing medium and high levels of V3Rs, respectively, may represent important events in the tumorigenesis of corticotroph cells.
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PMID:The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. 932 19

Prolonged exposure of vascular smooth muscle cells (VSMC) to vasoconstrictors such as vasopressin or angiotensin II induces hypertrophy and increases expression of muscle-specific genes including smooth muscle alpha-actin (SM-alpha-actin). These vasoconstrictors signal through G-proteins, including members of the Gq family. To further investigate the role of Gq family members, VSMC were transfected with a constitutively active mutant of a Gq family member, Galpha16 (Galpha16Q212L). Stable expression of Galpha16Q212L persistently stimulated phospholipase C, resulting in increased basal levels of inositol phosphates. These cells were hypertrophied and expressed elevated levels of SM-alpha-actin compared with wild-type VSMC or cells transfected with a control plasmid (Neo). SM-alpha-actin promoter activity was markedly increased in cells stably or transiently expressing Galpha16Q212L. Basal c-Jun-NH2-terminal kinase (JNK) activity was increased 3-9-fold in cells stably expressing Galpha16Q212L, while basal activity of the p42/44 mitogen-activated protein kinases (ERKs) was unaffected. Transient expression of a kinase inactive JNK kinase partially inhibited induction of SM-alpha-actin promoter activity in response to vasoconstrictors or expression of Galpha16Q212L. These results indicate that expression of constitutively active Galpha16 in VSMC mimics the effects of vasoconstrictors on hypertrophy and muscle-specific gene expression, and activation of JNK may play a role in these responses.
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PMID:Galpha16 mimics vasoconstrictor action to induce smooth muscle alpha-actin in vascular smooth muscle cells through a Jun-NH2-terminal kinase-dependent pathway. 932 15

Several agents that act through G-protein-coupled receptors and also stimulate phosphoinositide-specific phospholipase C (PI-PLC), including angiotensin II, vasopressin, norepinephrine, and prostaglandin (PG) F2alpha, activated the ERK1 (p44mapk) and ERK2 (p42mapk) members of the mitogen-activated protein (MAP) kinase family in primary cultures of rat hepatocytes, measured as phosphorylation of myelin basic protein (MBP) by a partially purified enzyme, immunoblotting, and in-gel assays. All these agonists induced a peak activation (two to threefold increase in MBP-phosphorylation) at 3-5 min, followed by a brief decrease, and then a sustained elevation or a second increase of the MAP kinase activity that lasted for several hours. Although all the above agents also stimulated PI-PLC, implicating a Gq-dependent pathway, the elevations of the concentration of inositol (1,4,5)-trisphosphate did not correlate well with the MAP kinase activity. Furthermore, pretreatment of the cells with pertussis toxin markedly reduced the MAP kinase activation by angiotensin II, vasopressin, norepinephrine, or PGF2alpha. In addition, hepatocytes pretreated with pertussis toxin showed a diminished MAP kinase response to epidermal growth factor (EGF). The results indicate that agonists acting via G-protein-coupled receptors have the ability to induce sustained activation of MAP kinase in hepatocytes, and suggest that Gi-dependent mechanisms are required for full activation of the MAP kinase signal transduction pathway by G-protein-coupled receptors as well as the EGF receptor.
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PMID:Activation of p42/p44 mitogen-activated protein kinase by angiotensin II, vasopressin, norepinephrine, and prostaglandin F2alpha in hepatocytes is sustained, and like the effect of epidermal growth factor, mediated through pertussis toxin-sensitive mechanisms. 957 80

Platelet-derived growth factor (PDGF), which is a potent mitogen for vascular smooth-muscle cells (VSMC), also inhibits the expression of specific smooth-muscle proteins, including smooth-muscle alpha-actin (SM-alpha-actin), in these cells. The goal of this study was to identify signalling pathways mediating these distinct effects. In rat aortic VSMC, PDGF caused a rapid activation of Ras and Raf, leading to the activation of mitogen-activated protein kinases (ERKs). Cells stably transfected with constitutively active Ras (H-Ras) expressed low levels of SM-alpha-actin protein. Arginine vasopressin, which stimulated SM-alpha-actin promoter activity in wild-type cells or controls (Neo; transfected with a plasmid lacking an insert), failed to do so in cells transiently expressing H-Ras. The effects of Ras on suppression of SM-alpha-actin expression were not mediated by the Raf/ERK pathway, since cells stably expressing constitutively active Raf (BxB-Raf) had normal levels of SM-alpha-actin protein, and stimulation of SM-alpha-actin promoter activity by vasopressin was unaffected in cells transiently expressing BxB-Raf. Furthermore a specific inhibitor of ERK activation had no effect on SM-alpha-actin expression. Exposure of wild-type VSMC to PDGF, or stable expression of Ras but not Raf, also resulted in constitutive increases in prostaglandin E2 production and cytosolic phospholipase A2 (cPLA2) activity, which was mediated by an increased expression of cPLA2 protein. Transient expression of cPLA2 in wild-type VSMC inhibited the stimulation of SM-alpha-actin promoter activity by vasopressin. These results suggest that PDGF-induced inhibition of SM-alpha-actin expression is mediated through a Ras-dependent/Raf independent pathway involving the induction of cPLA2 and eicosanoid production.
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PMID:Suppression of smooth-muscle alpha-actin expression by platelet-derived growth factor in vascular smooth-muscle cells involves Ras and cytosolic phospholipase A2. 958 46

Under conventional culture conditions, smooth muscle cells display their phenotypic modulation from a differentiated to a dedifferentiated state. Here, we established a primary culture system of smooth muscle cells maintaining a differentiated phenotype, as characterized by expression of smooth muscle-specific marker genes such as h-caldesmon and calponin, cell morphology, and ligand-induced contractility. Laminin retarded the progression of dedifferentiation of smooth muscle cells. Insulin-like growth factors (IGF-I and IGF-II) and insulin markedly prolonged the differentiated phenotype, with IGF-I being the more potent. In contrast, serum, epidermal growth factor, transforming growth factors, and platelet-derived growth factors potently induced dedifferentiation compared with angiotensin II, arginine-vasopressin, and basic fibroblast growth factor. Using the present culture system, we investigated signaling pathways regulating a phenotype of smooth muscle cells. In cultured cells, IGF-I specifically activated phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, protein kinase B, but not mitogen-activated protein kinases. Specific inhibitors of PI3-kinase (wortmannin and LY294002) induced dedifferentiation of smooth muscle cells even when they were cultured on laminin under IGF-I-stimulated conditions. The sole effect of laminin to retard the dedifferentiation was completely blocked by anti-IGF-I antibody, and laminin promoted the endogenous expression of IGF-I in cultured cells. The reduced promoter activity of the caldesmon gene induced by platelet-derived growth factor BB was overcome by the forced expression of the constitutive active form of PI3-kinase p110alpha catalytic subunit. These findings suggest that an IGF-I signaling pathway through PI3-kinase plays a critical role in maintaining a differentiated phenotype of smooth muscle cells.
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PMID:Differentiated phenotype of smooth muscle cells depends on signaling pathways through insulin-like growth factors and phosphatidylinositol 3-kinase. 978 87

The role of diacylglycerol (DAG) in hormonal induction of S phase was investigated in primary cultures of rat hepatocytes. In this model, several agonists that bind to G protein-coupled receptors act as comitogens when added to the cells soon after plating (i.e., in Go/early Gl phase), while the cells are most responsive to the mitogenic effect of epidermal growth factor (EGF) at 24-48 h of culturing (i.e., mid/late Gl). It was found that the cellular concentration of DAG rose markedly and progressively during the first 24 h of culturing. Exposure of the hepatocytes at 3 h to alpha1-adrenergic stimulation (norepinephrine with timolol), vasopressin, or angiotensin II further increased this rise, producing a sustained increase in the DAG level. Norepinephrine, which was the most efficient comitogen, produced the most prolonged DAG elevation. In contrast, no significant increase of DAG was found in response to EGF, neither at 3 nor at 24 h, using concentrations that markedly stimulated the ERK subgroup of the mitogen-activated protein kinases (MAPK) and DNA synthesis. Addition of Bacillus cereus phosphatidylcholine-specific phospholipase C (PC-PLC) strongly elevated DAG, while Streptomyces phospholipase D (PLD) increased phosphatidic acid (PA) but not DAG. B. cereus PC-PLC and the protein kinase C (PKC) activator tetradecanoyl phorbol-acetate (TPA), like norepinephrine, vasopressin, and angiotensin II, stimulated MAPK and enhanced the stimulatory effect of EGF on DNA synthesis. The PKC inhibitor GF109203X did not diminish the effect of EGF on MAPK or DNA synthesis, but strongly inhibited the effects of norepinephrine, vasopressin, angiotensin II, TPA and B. cereus PC-PLC on MAPK and almost abolished the enhancement by these agents of EGF-stimulated DNA synthesis. These results suggest that although generation of DAG is not a direct downstream response mediating the effects of the EGF receptor in hepatocytes, a sustained elevation of DAG with activation of PKC markedly increases the responsiveness to EGF. Mechanisms involving DAG and PKC seem to play a role in the comitogenic effects of various agents that bind to G protein-coupled receptors and activate the cells early in Gl, such as norepinephrine, angiotensin II, and vasopressin.
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PMID:Role of diacylglycerol (DAG) in hormonal induction of S phase in hepatocytes: the DAG-dependent protein kinase C pathway is not activated by epidermal growth factor (EGF), but is involved in mediating the enhancement of responsiveness to EGF by vasopressin, angiotensin II, and norepinephrine. 1039 90


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