Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the ability of epidermal growth factor (EGF) to regulate prostacyclin production by cultured A10 smooth muscle cells. EGF by itself had no effect on prostacyclin production, but it augmented the response to arg8-vasopressin. An AGF stimulation of prostacyclin production was also observed in the presence of the calcium ionophore A23187; it therefore seemed likely that the key event required for EGF to stimulate prostacyclin production might be an increase in the available cellular Ca2+. Studies with 45Ca2+ showed that vasopressin both mobilised Ca2+ from intracellular stores and increased the influx of extracellular Ca2+ into A10 cells. The increase in prostacyclin production caused by vasopressin and the augmentation by EGF were both abolished by TMB-8, an antagonist of Ca2+ mobilisation, by EGTA, a chelator of Ca2+ ions, or by incubating cultures in the absence of added Ca2+. These results were consistent with a central role for Ca2+ in the responses and showed that both intracellular and extracellular sources of Ca2+ were important for the triggering of prostacyclin production. The increases in prostacyclin production were only marginally affected by nifedipine, and no responses were seen (either in the absence or presence of EGF) when KCl was used to depolarise the cell membrane. These data indicated that uptake of Ca2+ ions via voltage-dependent channels was unlikely to be a major factor in the stimulation of prostanoid production. We conclude that the ability of EGF to stimulate prostacyclin production in A10 smooth muscle cells depends upon a concurrent stimulus that will increase available intracellular Ca2+ levels.
 ...
PMID:Epidermal growth factor stimulation of prostacyclin production by cultured aortic smooth muscle cells: requirement for increased cellular calcium levels. 254 10

Proximal tubules were prepared from rat kidney cortex by collagenase digestion and purified by Percoll gradient centrifugation. Their enrichment was estimated by comparing the specific activities of various cell-specific enzymes in homogenates of renal cortex and of the isolated tubules. The tubules were cultured in a 50:50 mixture of Dulbecco's modified Eagle's and Ham's F12 media supplemented with insulin, transferrin, epidermal growth factor, hydrocortisone, and prostaglandin E1. After 2 to 3 d an extensive outgrowth of epithelial cells developed from the attached tubules. After 5 to 7 d near confluent monolayers were obtained. Hormonal responsiveness, marker enzyme activities, and transport properties were determined to further characterize the primary cultures. The cultured cells exhibited increased cyclic AMP production in response to parathyroid hormone but not calcitonin or vasopressin, consistent with the absence of cells derived from distal and collecting tubules. The cells also retained significant levels of 25-hydroxyvitamin D3-1 alpha-hydroxylase, alkaline phosphatase, and gamma-glytamyl-transpeptidase, three enzymes that are primarily associated with the proximal tubule. The cultured epithelial cells also exhibit a Na+-dependent phosphate and glucose transport systems. Therefore, the cells retain many functional properties that are characteristic of proximal tubules. Thus, the primary cultures should be suitable for the study of processes that occur specifically within this segment of the rat nephron.
 ...
PMID:Characterization of primary cell cultures derived from rat renal proximal tubules. 254 89

We have previously reported that the potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) and a factor from fetal calf serum (FCS) markedly enhance the transformation of mouse C3H 10T1/2 and Rat 6 fibroblasts, when added to cultures following transfection with plasmid pT24 DNA that contains an activated c-Ha-ras oncogene. In the present study, we examined possible enhancing or inhibiting effects of various chemicals on the transformation of Rat 6 fibroblasts by T24 DNA when tested in the presence of calf serum, calf serum plus TPA or FCS. We found that, like TPA, the chemicals mezerein, 1-oleoyl-2-acetylglycerol, and phospholipase C increased the yield of T24-induced foci, thus further implicating protein kinase C as a critical constituent in this process. Low concentrations (10(-6)-10(-7)M) of retinoic acid (both trans and 13-cis) also stimulated cell transformation. Several compounds inhibited T24-induced transformation. These included nontoxic concentrations of the calcium ionophore A23187, indomethacin, and epsilon-amino-n-caproic acid. Compounds that failed to exert a significant reproducible effect included vasopressin, vitamin D3, selenium, antipain, Bowman-Birk inhibitor, vitamin B12, epidermal growth factor, platelet-derived growth factor, insulin, and transferrin. These findings suggest that this simple in vitro system might be useful for detecting enhancers and inhibitors of ras oncogene-induced cell transformation and also elucidating their mechanisms of action.
 ...
PMID:Effects of various chemical agents on the transformation of rat fibroblasts by an activated c-Ha-ras oncogene. 266 19

The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase.
 ...
PMID:Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells. 269 Aug 29

A10 cultured smooth muscle cells from rat embryonic thoracic aorta bound 125I-labelled epidermal growth factor (125I-EGF), and responded to EGF by an increase in DNA synthesis. Scatchard analysis of binding data obtained at 4 degrees C showed curvilinearity consistent with there being two affinity classes of binding site. The amount of 125I-EGF that bound was decreased by treatment of the A10 cells at 37 degrees C with [Arg8]vasopressin or with 5-hydroxytryptamine (5-HT). Scatchard analysis of binding (at 4 degrees C after pretreatment at 37 degrees C) revealed this effect to be due to a loss of the high-affinity component of 125I-EGF binding, with no change in total receptor number. The presence of vasopressin or 5-HT raised the concentration of EGF required for the stimulation of DNA synthesis. Cultured A10 aortic smooth muscle cells therefore have receptors for EGF that mediate an increase in cell proliferation. EGF receptor function is modified by vasopressin and 5-HT, probably as a consequence of their effects on EGF receptor affinity.
 ...
PMID:Heterologous regulation of EGF receptor function in cultured aortic smooth muscle cells. 271 68

Exposure of a nontransformed, continuous line of epithelial cells derived from rat liver (WB cells) to epidermal growth factor, angiotensin II, [Arg8]vasopressin, and epinephrine resulted in rapid accumulation of the inositol phosphates (InsP) InsP1, InsP2, and InsP3. Although short-term (5-60 min) pretreatment of WB cells with the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) markedly attenuated InsP accumulation in response to all agonists, the inhibitory effects on the InsP response were lost after 2 h incubation with PMA; and, with extended (6-24 h) preincubation, a time-dependent potentiation of the InsP response to angiotensin II, epidermal growth factor and [Arg8]vasopressin was observed. The InsP response during a 15-min challenge with angiotensin II in cells pretreated for 18 h with 600 nM and 10 microM PMA was increased by 2-3-fold and 4-6-fold, respectively. Long-term (18 h) treatment with 600 nM and 10 microM PMA caused a similar 90-100% loss of measurable Ca2+/phospholipid-dependent enzyme (protein kinase C) activity in cytosolic and soluble particulate fractions. The effects of long-term PMA pretreatment do not represent a general enhancement of hormone responsiveness since the InsP response to epinephrine was not affected. In control cells, the InsP response to angiotensin II and epinephrine desensitized very rapidly. Long-term pretreatment with PMA greatly reduced the contribution of agonist-induced desensitization to the angiotensin II response; in contrast, the extent of desensitization occurring during incubation of WB cells with epinephrine was unaltered by long-term treatment with PMA suggesting that an additional mechanism may be involved in alpha 1-adrenergic receptor desensitization. No PMA-induced change in resting levels of [3H]phosphoinositides or the metabolism of exogenous [3H]inositol 1,4,5-trisphosphate by WB homogenates occurred. Stimulation of InsP formation in intact cells by NaF and activation of phospholipase C by GTP gamma S in membranes both were unaltered by short-term or long-term PMA pretreatment. These data are consistent with the idea that following long-term treatment of WB cells with PMA, the occurrence of agonist-induced desensitization of receptors linked to the phosphoinositide/Ca2+ signaling system is reduced, apparently at least in part due to the loss of contribution of a negative feedback regulatory role of protein kinase C.
 ...
PMID:Long-term phorbol ester treatment down-regulates protein kinase C and sensitizes the phosphoinositide signaling pathway to hormone and growth factor stimulation. Evidence for a role of protein kinase C in agonist-induced desensitization. 283 90

Calf serum induced the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney (NRK) cells transformed by a temperature-sensitive Kirsten murine sarcoma virus (tsK-NRK cells). Various growth factors known to induce the phospholipase C reactions in other cell types, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, thrombin, vasopressin, bombesin, cholecystokinin, and prostaglandin F2 alpha, did not induce phospholipase C reactions in the transformed NRK cells. Furthermore, noradrenaline, histamine, dopamine, angiotensin II, carbachol, and tumor growth factor-beta did not induce phospholipase C reactions. However, serotonin did induce phospholipase C reactions. The amount of serotonin contained in the calf serum was sufficient to support 50% of the activity promoted by the serum itself, and calf serum-induced phospholipase C reactions were inhibited to 10-20% of the original level by ketanserin and methysergide, known to be antagonists for the serotonin receptors. Dialysis almost completely removed serotonin from calf serum and reduced the serum-induced phospholipase C reactions. Moreover, the phospholipase C reactions induced by calf serum and serotonin were inhibited by pretreatment of the cells with pertussis toxin or 12-O-tetradecanoylphorbol-13-acetate. These results indicate that serotonin is one of the major serum factors inducing phospholipase C-mediated hydrolysis of phosphoinositides in transformed NRK cells. Serotonin induced phospholipase C reactions not only in tsK-NRK cells but also in nontransformed NRK cells. However, serotonin did not induce these reactions in Swiss 3T3 cells or NIH 3T3 cells.
 ...
PMID:Serotonin as a major serum factor inducing the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney cells. 284 56

The influence of exogenous endotoxin pretreatment on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats with midline laparotomy and liver manipulation as the sham control. Animals were pretreated with endotoxin at a dose of 33 micrograms/100 g sc or iv 24 h before surgery and then fasted. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA, and plasma levels of hepatotrophic factors were measured by radioimmunoassay or radioreceptor assay. Systemic endotoxemia occurred after exogenous endotoxin administration as well as after partial hepatectomy due to absorption of exogenous endotoxin from the gut into the portal circulation as determined by quantitative chromogenic lysate assay of perchloric acid-extracted plasma samples. Alterations in putative hepatotrophic factors, including insulin, glucagon, epidermal growth factor, vasopressin, and triiodothyronine, were remarkable similar in response to endotoxemia by exogenous endotoxin administration and by endogenous endotoxin absorption from the gut after partial hepatectomy. Our hypothesis purports that gut-derived systemic endotoxemia elicits hepatotrophic factor secretion for liver regeneration after partial hepatectomy and that endotoxin pretreatment expedites the hepatotrophic factor response, thus accelerating DNA synthesis in the proliferating liver after 67% resection.
 ...
PMID:Gut-derived endotoxin elicits hepatotrophic factor secretion for liver regeneration. 286 2

The effects of some chemically defined growth factors on the locomotion of quiescent Swiss 3T3 fibroblasts have been studied. A computer digitiser has been used to facilitate recording the paths followed by cells in time-lapse films; this method allows 500 cell-hours to be recorded in 1 h of real time. Individual cells in the same culture vary widely in speed. This variation is not associated with the positions of the cells in the cell cycle; a small deceleration which seems to occur in G2 cannot account for any significant part of the variation seen. Nor is it related to the time elapsing before the cell divides, although this is equally variable; the speed and age at division of particular cells appear to be entirely independent of one another. Nevertheless, good reproducibility is seen between the mean speeds of large numbers of cells from the same type of culture. The mean speed of quiescent cells is less than 2 microns/h. A mixture of epidermal growth factor (EGF) and vasopressin, in the presence of insulin, is known to be a potent promoter of proliferation in this system. We have found it to increase speed to 30 microns/h. Agents which stimulate the cellular level of cAMP are also known to be potent promoters of proliferation in the presence of insulin. We have found these agents to be inhibitors of locomotion; several cycles of cell division take place while the cells move at a speed no greater than that seen in the presence of cytochalasin B (CB) or colchicine. These findings therefore give further support to the idea that there may be two different classes of growth-promoting factors, with major differences in their mode of action. They show that some members of these two different classes have opposite effects on motility.
 ...
PMID:Stimulating the proliferation of quiescent 3T3 fibroblasts by peptide growth factors or by agents which elevate cellular cyclic AMP level has opposite effects on motility. 298 Nov 76

Recent studies with viral oncogene tyrosine kinases have suggested that these kinases may phosphorylate phosphoinositides and diacylglycerol. Since the receptors for insulin and epidermal growth factor (EGF) also possess tyrosine kinase activity, we have investigated possible effects of insulin and EGF on phosphoinositide metabolism in rat liver plasma membranes and rat hepatocytes. In plasma membranes prepared from rats injected 18 h prior with [3H]myo-inositol or incubated with [gamma-32P]ATP, phosphatidylinositol-4-P and phosphatidylinositol-4,5-P2 were formed, but there were no effects of either insulin or EGF although these agents stimulated protein tyrosine phosphorylation. In hepatocytes incubated with [3H]myo-inositol, label was incorporated into phosphatidylinositol, phosphatidylinositol-4-P, and phosphatidylinositol-4,5-P2, but there was no effect of insulin. Incubation of hepatocytes with [3H]myo-inositol plus insulin or EGF for 2 h also did not alter the formation of [3H]myo-inositol-1,4,5-P3 from [3H]phosphatidylinositol-4,5-P2 induced by vasopressin. These findings suggest that the tyrosine kinase activity of liver insulin and EGF receptors is not important in phosphoinositide formation.
 ...
PMID:Insulin and epidermal growth factor do not affect phosphoinositide metabolism in rat liver plasma membranes and hepatocytes. 298 1


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