Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our studies of normal and neoplastic growth regulation, we have compared growth factor induced second messenger response and mitogenic activity in a rat hepatocarcinogenesis model. Inositol phosphate (IP) turnover was measured by incubating the cells with [3H]inositol and stimulating them with either epidermal growth factor, diferric transferrin, ferricyanide, vasopressin, norepinephrine, angiotensin II or bombesin for 2 min. The IPs formed were separated on HPLC. Mitogenic responses were monitored by bromodeoxyuridine uptake and labeling index. IP turnover was stimulated by vasopressin, norepinephrine and angiotensin II in both normal and nodular cells, but not by the other four agonists tested. The IP response was somewhat lower in cells from liver nodules. All compounds except bombesin were mitogenic to both nodular cells and cells from normal rats of different ages, with epidermal growth factor inducing the largest mitogenic response. Bombesin, on the other hand, had only a minor effect on normal cells, but induced a pronounced mitogenic response in nodular cells. In normal rats, the cells' ability to respond to growth stimulation decreased with increasing rat age. In this respect, nodular cells behaved in a way more like young normal cells than their age-matched controls. Taken together, these data support the view of liver nodules being a more autonomous cell population, with increased sensitivity to growth factors and possibilities for autocrine growth stimulation.
...
PMID:Growth factor induced mitogenic effects and inositol phosphate responses in primary hepatocyte cultures from normal rat liver and rat liver nodules. 792 74

We analyzed the effect of growth factors on the localization of the 80-kDa acidic myristoylated alanine-rich C-kinase substrate (80-kDa MARCKS), the major protein kinase C (PKC) substrate, in Swiss 3T3 fibroblasts. Virtually all 80-kDa MARCKS of quiescent cultures of these cells was membrane bound. However, within 40 min after addition of bombesin (10 nM) to these cells, the content of 80-kDa MARCKS in the cytoplasmic fraction increased 25-fold. Phosphorylated 80-kDa MARCKS was detectable in the cytoplasmic fraction as early as 30 s after addition of bombesin and the translocation was sustained for 6 h i.e. until 80-kDa MARCKS became down-regulated. The ability of bombesin to stimulate translocation of 80-kDa MARCKS was dose-dependent (concentration required to produce 50% of the effect was 0.6 nM bombesin) and was abolished by the specific antagonist [Leu14,13 psi 14CH2NH]bombesin. Furthermore, platelet-derived growth factor (PDGF) stimulated a dose-dependent (concentration required to produce 50% of the effect was 3 ng/ml) translocation which was comparable to that induced by bombesin in terms of kinetics and magnitude. Translocation was independent of continuous protein synthesis, but dependent on active PKC. Depletion or inhibition of PKC activity abolished the 80-kDa MARCKS translocation induced by either bombesin or PDGF. Furthermore, the neuropeptides beta-endothelin, bradykinin, and vasopressin, which are known to stimulate PKC activity, also promoted translocation. In contrast, epidermal growth factor, insulin and forskolin, which do not activate PKC, failed to cause such an effect. Translocation of 80-kDa MARCKS was also observed in Rat1 cells treated with phorbol ester, PDGF and beta-endothelin. We conclude that the translocation of 80-kDa MARCKS from the membrane to the cytosol is an early response to a variety of growth-promoting factors that stimulate PKC through different signal-transduction pathways.
...
PMID:Bombesin, endothelin and platelet-derived growth factor induce rapid translocation of the myristoylated alanine-rich C-kinase substrate in Swiss 3T3 cells. 795 68

The role of heterotrimeric GTP-binding proteins in the process of store-operated Ca2+ inflow in hepatocytes was investigated by testing the ability of pertussis toxin to inhibit thapsigargin- and 2,5-di-tert-butylhydroquinone (DBHQ)-induced bivalent cation inflow. Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited markedly inhibited rates of both Ca2+ and Mn2+ inflow when these were stimulated by vasopressin, angiotension II, epidermal growth factor, thapsigargin and DBHQ. Pertussis toxin had little effect on the basal intracellular free Ca2+ concentration ([Ca2+]i), basal rates of Ca2+ and Mn2+ inflow, the abilities of vasopressin, angiotensin II, thapsigargin and DBHQ to induce the release of Ca2+ from intracellular stores, and the maximum value of [Ca2+]i reached following agonist-induced release of Ca2+ from intracellular stores. It is concluded that store-operated Ca2+ inflow in hepatocytes employs a slowly ADP-ribosylated trimeric GTP-binding protein and is the physiological mechanism, or one of the physiological mechanisms, by which vasopressin and angiotensin stimulate plasma membrane Ca2+ inflow in this cell type.
...
PMID:Evidence from studies with hepatocyte suspensions that store-operated Ca2+ inflow requires a pertussis toxin-sensitive trimeric G-protein. 798 Mar 92

Glucose depressed DNA synthesis in rat hepatocytes in primary culture. As compared to controls cultured with 5.6 mM glucose, maximal (> or = 75%) inhibition was obtained at 20-30 mM, and half-maximal effect at 10-15 mM. Comparison of D- and L-glucose showed that the effect was specific for the D-form. Maximal inhibition required the presence of glucose during the first 24 hours of culture. The expression of the c-myc gene was reduced when the hepatocytes were cultured in the presence of elevated glucose. The responses to epidermal growth factor, insulin and vasopressin, in terms of percentual stimulation of DNA synthesis, were qualitatively similar at 5.6 and 16.8 mM glucose, while glucagon stimulated more strongly when the glucose concentration was increased; glucagon at concentrations > or = 1 nM reversed the inhibition by glucose. 8-Br-cAMP mimicked the effect of glucagon. These results suggest that an increase in the level of glucose depresses hepatocyte DNA synthesis. The effect is associated with lowered expression of the c-myc gene and is counteracted by cAMP.
...
PMID:Elevated glucose concentrations inhibit DNA synthesis and expression of c-myc in cultured hepatocytes. 806 Mar 30

Mitogen-activated protein (MAP) kinase is a widely expressed protein serine/threonine kinase that serves as a convergence point for many signaling pathways including receptor tyrosine kinases, G protein-coupled receptors, and protein kinase C (PKC). The hormonal regulation of MAP kinase was studied in cultured established rat inner medullary collecting tubule (RIMCT) cells. Neither vasopressin nor beta-adrenergic agonists stimulated MAP kinase, despite clear stimulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. In contrast, carbachol, ATP, and epidermal growth factor (EGF), which are known to antagonize vasopressin action in the RIMCT, stimulated the MAP kinase pathway. This stimulation was mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, which directly activates PKC. The potency with which EGF and carbachol activated MAP kinase was similar to the potency with which they inhibited vasopressin-stimulated cAMP accumulation. To assess the role of Gi proteins in these stimulatory events, RIMCT cells were pretreated with pertussis toxin to inhibit Gi-mediated signaling. Pertussis toxin did not influence ATP- or EGF-stimulated MAP kinase, but completely inhibited carbachol stimulation, suggesting that Gi proteins mediate muscarinic stimulation. Prolonged exposure of RIMCT cells to high phorbol ester concentrations to downregulate PKC ablated carbachol- and ATP-stimulated MAP kinase, but not EGF-stimulated MAP kinase, suggesting that PKC is a component of the network involved in MAP kinase activation by purinergic and muscarinic agonists. Investigation of the sidedness of the hormonal stimulations indicated that EGF-stimulated MAP kinase was highly polarized, occurring exclusively from the basolateral surface, whereas carbachol stimulated MAP kinase similarly from either cell surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Hormonal regulation of MAP kinase in cultured rat inner medullary collecting tubule cells. 809 50

Epidermal growth factor and transforming growth factor alpha stimulated DNA synthesis in primary cultures of adult rat hepatocytes. Neurotensin amplified epidermal growth factor-stimulated or transforming growth factor alpha-stimulated DNA synthesis by three- to eightfold. Neurotensin by itself did not stimulate DNA synthesis. Amplification of DNA synthesis by neurotensin was observed as low as 10(-10) M, and it was increased in a dose-dependent manner with maximal effects at 10(-8) M. These results were obtained when hepatocytes were cultured in Williams' medium E, but not in Leibovitz L-15 medium, suggesting that a minor component(s) in the medium is required for hepatocytes to fully respond to neurotensin. Neurotensin effect on DNA synthesis was observed not only in normal rat hepatocytes but also in partially hepatectomized rat hepatocytes, although its effect was stronger in normal hepatocytes. Amplified DNA synthesis was inhibited by transforming growth factor beta. Secondary mitogens (co-mitogens) such as insulin, vasopressin, or angiotensin II interacted additively with low concentrations of epidermal growth factor as well as with neurotensin. Neurotensin-related peptides such as kinetensin or neuromedin-N, which was released from blood plasma by pepsin digestion, did not have this amplifying effect on DNA synthesis at any concentrations tested. Neurotensin mRNA was found in several organs including brain and intestine, but not liver. These results suggest that neurotensin can be regarded as a new secondary mitogen and that it may be involved in cell proliferation, including regenerating liver as a gastrointestinal hormone and/or a neurotransmitter.
...
PMID:Stimulation of hepatocyte DNA synthesis by neurotensin. 810 58

In this study, we have examined the relationship between epidermal growth factor (EGF)-induced tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and its translocation from the cytosol to the Triton X-100-insoluble cytoskeleton fraction in rat hepatocytes. The translocation of PLC-gamma 1 was specific for EGF stimulation, because a similar effect was not observed with insulin or vasopressin. EGF caused a transient increase of PLC activity in the cytoskeleton fraction which could be abolished by immunoprecipitating PLC-gamma 1. Tyrosine phosphorylated PLC-gamma 1 was seen only in the cytoskeleton fraction, suggesting that tyrosine phosphorylation is required for PLC-gamma 1 translocation to the cytoskeleton. This process may involve binding of PLC-gamma 1 to actin filaments, since actin was immunoprecipitated together with PLC-gamma 1 in the cytoskeleton after EGF treatment. EGF-induced translocation of PLC-gamma 1 to the cytoskeleton was not inhibited by pertussis toxin, but Gi alpha was translocated in an EGF-dependent manner, suggesting that the interaction of PLC-gamma 1 with its activated Gi-protein is downstream from both PLC-gamma 1 tyrosine phosphorylation and its translocation to the cytoskeleton. Taken together, the present studies indicate that EGF-induced tyrosine phosphorylation of PLC-gamma 1, its association with the cytoskeleton, and its interaction with activated Gi alpha protein are all obligatory for PLC-gamma 1 activation in hepatocytes.
...
PMID:Epidermal growth factor-induced activation and translocation of phospholipase C-gamma 1 to the cytoskeleton in rat hepatocytes. 812 25

The roles of heterotrimeric GTP-binding regulatory proteins (G-proteins) and inositol polyphosphates in the mechanism by which vasopressin stimulates Ca2+ inflow in hepatocytes were investigated by using single cells loaded with fura2 by microinjection. Vasopressin-stimulated Ca2+ inflow was mimicked by microinjection of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) or guanosine 5'-[beta gamma-imido]triphosphate to the cells, but not adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine 5'-[beta-thio]diphosphate (GDP[S]). Extracellular Gd3+ (5 microM) inhibited both vasopressin- and GTP[S]-stimulated Ca2+ inflow. GDP[S], but not GMP, administered to hepatocytes by microinjection, completely inhibited vasopressin-stimulated Ca2+ inflow and partially inhibited vasopressin-induced release of Ca2+ from intracellular stores. The microinjection of pertussis toxin had no effect either on the release of Ca2+ from intracellular stores or on Ca2+ inflow induced by vasopressin, but completely inhibited changes in these processes induced by epidermal growth factor (EGF). Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited no vasopressin- or GTP[S]-stimulated Ca2+ inflow, whereas the vasopressin-stimulated release of Ca2+ from intracellular stores was similar to that observed for control cells. Heparin or ATP[S] inhibited, or delayed the onset of, both vasopressin-induced release of Ca2+ from intracellular stores and vasopressin-stimulated Ca2+ inflow. Vasopressin-induced oscillations in intracellular [Ca2+] were observed in some heparin-treated cells. It is concluded that the stimulation by vasopressin of Ca2+ inflow to hepatocytes requires inositol 1,4,5-trisphosphate (InsP3) and, by implication, the pertussis-toxin-insensitive G-protein required for the activation of phospholipase C beta [Taylor, Chae, Rhee and Exton (1991) Nature (London) 350, 516-518], and another G-protein which is slowly ADP-ribosylated by pertussis toxin and acts between InsP3 and the putative plasma-membrane Ca2+ channel. EGF-stimulated Ca2+ inflow involves at least one G-protein which is rapidly ADP-ribosylated and is most likely required for InsP3 formation.
...
PMID:A slowly ADP-ribosylated pertussis-toxin-sensitive GTP-binding regulatory protein is required for vasopressin-stimulated Ca2+ inflow in hepatocytes. 817

Cicletanine sulfate was tested on bicarbonate-dependent pHi changes in cultured vascular smooth muscle (A10 line). Cicletanine sulfate exhibited double reactivity with regard to the cell alkalinization induced by bicarbonate uptake. The analysis of 11 concentration-response curves revealed a high reactivity component (IC50 approximately 3.5 x 10(-8) mol/L) and a weak reactivity component (IC50 approximately 4 x 10(-4) ml/L). Regarding the cell acidification induced by bicarbonate extrusion, cicletanine sulfate exhibited a single high reactivity component (IC50 = 5.9 +/- 2.9 x 10(-7) mol/l; mean +/- SD, n = 7). The high and weak reactivity sites were both sensitive to DIDS. Analysis of the data strongly suggested that the highly reactive site corresponds to a sodium-independent (Cl-/HCO3-] exchanger, which catalyzes net bicarbonate efflux, and the weak-reactivity site corresponds to the inwardly directed sodium-dependent [Cl-/HCO3-] exchanger. Three cell growth factors--epidermal growth factor, arginine-vasopressin, and insulin--were able to stimulate the sodium-independent [Cl-/HCO3-] exchanger in A10 cells. Finally, cicletanine sulfate (30 mumol/L) partially inhibited serum-dependent A10 cell growth. In conclusion, cicletanine sulfate and cell growth factors exert opposite effects (inhibition and stimulation, respectively) on the sodium-independent [Cl-/HCO3-] exchanger in cultured vascular smooth muscle. The effect of cicletanine sulfate on the sodium-independent [Cl-/HCO3-] exchanger may account for the ability of cicletanine to favorably alter vascular pathology in spontaneously hypertensive rat (SHR) models.
...
PMID:Opposite effects of cell growth factors and cicletanine sulfate on the sodium-independent [Cl-/HCO3-] exchange in cultured vascular smooth muscle. 821 30

The inositol trisphosphate receptor (IP3R) in brain has been shown to be a substrate for several different protein kinases in vitro. We have studied the phosphorylation of the IP3R in intact cells by using isolated hepatocytes and an antibody to immunoprecipitate the receptor protein from detergent extracts. Stimulation of 32P-labeled hepatocytes with glucagon or N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP) markedly increased phosphorylation of the IP3R. However, no increase was observed in response to angiotensin II, vasopressin, 12-O-tetradecanoyl-phorbol-13-acetate, or epidermal growth factor. The kinetics of phosphorylation in response to glucagon was both rapid and transient. In agreement with previous studies, physiological concentrations of Ca2+ stimulated D-myo-inositol 1,4,5-trisphosphate (IP3) binding to permeabilized hepatocytes (Pietri, F., Hilly, M., and Mauger, J.-P. (1990) J. Biol. Chem. 265, 17478-17485). Pretreatment of cells with db-cAMP had no effect on binding in the absence of added Ca2+ but enhanced binding measured in the presence of basal low concentrations (0.16-0.25 microM) of Ca2+ and decreased the concentration of Ca2+ required for half-maximal stimulation. The effect of db-cAMP was associated with an increase in affinity of the IP3 binding site without a change in maximum number of binding sites. Preincubation of intact hepatocytes with okadaic acid alone produced an increase in basal phosphorylation of the IP3R, and maximal phosphorylation of the receptor was observed in the presence of both okadaic acid and db-cAMP. However, okadaic acid blocked the effect of db-cAMP and inhibited the effect of Ca2+ on IP3 binding. Detergent-solubilized binding sites were already fully activated and insensitive to modulation by Ca2+ or cAMP-dependent protein kinase. It is proposed that the receptor in native membranes is inhibited and that Ca2+ and cAMP-dependent protein kinase may act to relieve this inhibition.
...
PMID:Phosphorylation of the inositol trisphosphate receptor in isolated rat hepatocytes. 822 22


<< Previous 1 2 3 4 5 6 7 8 9 10

---