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)

Insulin and various growth factors (epidermal growth factor (EGF), insulin-like growth factor, fibroblast growth factor, and transforming growth factor alpha), which fail to modify the resting [Ca2+]i in PC12 rat pheochromocytoma and SKNBE human neuroblastoma cells when administered alone, became capable of inducing [Ca2+]i increases when administered a few (4-20) min after another agent, bradykinin. The latter peptide, working through a B2 receptor, caused hydrolysis of polyphosphoinositides and a large, biphasic [Ca2+]i transient (an initial (1-2 min) spike, originated primarily from intracellular stores, followed by a steady-state elevation dependent on Ca2+ influx). Priming by bradykinin of the growth factor effects was quickly dissipated by the addition of a B2 blocker. Activation of other receptors coupled to polyphosphoinositide hydrolysis: muscarinic and purinergic (in PC12 and SKNBE cells); bombesin and vasopressin receptors (in Swiss 3T3 cells), was without effect in priming. Bradykinin-primed, growth factor-induced [Ca2+]i rises in PC12 cells appeared after a 20-30-s delay; they were relatively small, but persistent; their concentration dependence was similar to that of other effects of the factors; and they included both release of Ca2+ from intracellular stores and stimulation of Ca2+ influx, preceded (in PC12 cells) by a transient increase of polyphosphoinositide hydrolysis. Thus the effect of growth factors (possibly dependent on the tyrosine kinase activity of their receptors) consisted in the reinforcement of the transmembrane signaling at B2 receptors. This is the first direct demonstration of a [Ca2+]i rise induced by insulin and insulin-like growth factor-I, and of such an effect of EGF in cell types endowed with a small number of specific EGF receptors.
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PMID:Reinforcement of signal generation at B2 bradykinin receptors by insulin, epidermal growth factors, and other growth factors. 253 35

The primary action of a family of mitogens including bombesin, bradykinin, vasopressin and alpha-thrombin is to activate the hydrolysis of polyphosphoinositides. Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by phospholipase C is mediated through coupling of surface receptors to a GTP-binding protein (Gp protein) which, in some cells, is inactivated by the toxin of Bordetella pertussis. It is not known whether this signalling pathway is involved in initiating DNA replication, whereas it has been firmly established that reinitiation of DNA synthesis can be triggered without activation of PtdIns(4,5)P2 hydrolysis by, for example, EGF (epidermal growth factor), FGF (fibroblast growth factor) and insulin/IGF-I (insulin-like growth factor-I), members of a class of mitogens known to activate receptor tyrosine kinases. Taking advantage of the fact that Chinese hamster lung fibroblasts respond to either class of mitogens and that their Gp protein appears to be sensitive to pertussis toxin, we have now analysed the toxin's effect on reinitiation of DNA synthesis and find that it inhibits up to 95% of thrombin-induced mitogenicity without affecting EGF- or FGF-induced DNA synthesis and proliferation. These findings strongly suggest that activation of PtdIns(4,5)P2-phospholipase C has a determinant function in growth control, and confirm the existence of alternative growth factor-signalling pathways independent of polyphosphoinositide breakdown.
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PMID:Two growth factor signalling pathways in fibroblasts distinguished by pertussis toxin. 303 10

In pituitary-dependent hyperadrenocorticism (Cushing's disease), the disturbed regulation of ACTH secretion is associated with neoplastic transformation of corticotropic cells. As these two phenomena are almost indissolubly connected, it is of prime importance to elucidate the factor(s) that induce corticotropic cell proliferation. Here we report on the effects of hypophysiotrophic hormones and intrapituitary growth factors on the proliferation and hormone secretion of the murine corticotropic tumour cell line AtT20/D16v, as measured by DNA content, and ACTH concentration in culture media. In addition, sensitivity to the inhibitory effect of cortisol was assessed under various conditions. Corticotropin releasing hormone (CRH) and vasopressin (AVP) induced proliferation of AtT20-cells. In contrast to that caused by AVP, the CRH-induced proliferation was associated with increased ACTH secretion, which could be inhibited by cortisol. Insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) also stimulated the proliferation of AtT20-cells. The proliferation of AtT20-cells was significantly inhibited by cortisol in all tests. The IGF-I-induced proliferation was the least sensitive to inhibition by cortisol. The growth factors did not stimulate ACTH secretion but IGF-I differed in that it prevented the inhibition of basal ACTH secretion by cortisol. Additional experiments (Western ligand blot analysis) concerning the relative insensitivity of IGF-I induced proliferation to inhibition by cortisol revealed that IGF-I increased the concentration of a 29 kDa IGF binding protein (IGFBP) in the culture medium. The concentration of the 29 kDa IGFBP was slightly decreased by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proliferation of the murine corticotropic tumour cell line AtT20 is affected by hypophysiotrophic hormones, growth factors and glucocorticoids. 754 6

We found low T3 concentrations in rat brown adipocytes differentiated in vitro. This might be due to the high metabolic rate of T3, possibly caused by elevated type III iodothyronine 5-deiodinase activity (5DIII), induced by serum growth factors. We tested the ability of several growth factors to induce 5DIII activity. Epidermal growth factor and basic and acidic fibroblast growth factors produced a strong induction of 5DIII activity (25, 45-, and 50-fold, respectively). This process required gene transcription and de novo protein synthesis. The half-life of 5DIII was approximately 3 h. Heparin was required for full acidic fibroblast growth factor activity. Platelet-derived growth factor, vasopressin, and insulin-like growth factor-I induced lower 5DIII activities (3- to 6-fold). Vasopressin amplified basic fibroblast growth factor and epidermal growth factor inductions when used at submaximal doses. We found a Km of 22.5 nM using T3 as substrate. Although brown adipose tissue has undetectable 5DIII activities in vivo, the present data explain the low T3 concentrations found in cultured rat brown adipocytes and suggest that growth factors, by stimulating 5DIII, may lead to low T3 concentrations and indirectly inhibit the expression of some genes regulated by T3, e.g. the rat uncoupling protein.
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PMID:Presence of growth factors-induced type III iodothyronine 5-deiodinase in cultured rat brown adipocytes. 766 75

Colonies of small hepatocytes appeared after the culture of primary adult rat hepatocytes for 4 days in serum-free Dulbecco's modified Eagle's medium containing 10 mM nicotinamide and 10 ng/ml of epidermal growth factor (EGF), acidic and basic fibroblast growth factors (FGF), hepatocyte growth factor (HGF), or transforming growth factor-alpha (TGF-alpha). Every colony consisted of cells that each had a single nucleus and a higher nucleus/cytoplasm ratio than surrounding hepatocytes, and immunocytochemically the cells induced by any mitogen were stained with albumin, transferrin, cytokeratin-8 and -18. But these cells expressed neither cytokeratin-7 nor -19. When 6 x 10(5) cells were plated on 35-mm dishes, about 15 colonies per 1,000 attached cells were observed in the cultures treated with EGF, HGF, and TGF-alpha. Although FGFs could also induce colonies, their number was less than half of the number induced by EGF. Furthermore, the numbers of colonies induced by the combinations of EGF+HGF, EGF+TGF-alpha, and HGF+TGF-alpha were not different from those of the colonies induced by each mitogen alone. To examine the ability of co-mitogenic factors to induce small-cell colonies, angiotensin-II, insulin-like growth factor-I, norepinephrine, tumor necrosis factor, and vasopressin were used. In the cells cultured without EGF, these co-mitogens neither stimulated DNA synthesis nor induced colonies. On the other hand, in cells cultured with both EGF and each co-mitogen, although the DNA synthesis of the hepatocytes was enhanced, the number of colonies detected was not significantly different from the number which EGF alone could induce. These results showed that the small-cell colonies in primary cultures of rat hepatocytes were inducible by EGF, HGF, TGF-alpha, or FGFs and that the co-mitogens did not influence the formation of the small-cell colonies.
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PMID:Effects of mitogens and co-mitogens on the formation of small-cell colonies in primary cultures of rat hepatocytes. 825 57

Extrinsic factors such as hypothalamic hormones or intrapituitary growth factors may stimulate clonal expansion of a genomically altered cell and therefore play a role in pituitary tumorigenesis. Here we report on the effects of the hypophysiotrophic hormones corticotrophin-releasing hormone (CRH) and vasopressin (AVP) and the intrapituitary growth factor insulin-like growth factor-I (IGF-I) on the proliferation of, as measured by the bromodeoxyuridine labelling index, and ACTH secretion by normal canine pituitary cells and corticotrophic adenoma cells of dogs with pituitary-dependent hyperadrenocorticism. The sensitivity to inhibition by cortisol was analysed under various conditions. Under basal conditions, no significant differences were found in the bromodeoxyuridine labelling indices between control cells and tumour cells. CRH, AVP, IGF-I and cortisol had no effect on the proliferation of canine pituitary cells or canine corticotrophic adenoma cells. In contrast with normal pituitary cells, the proliferation of corticotrophic adenoma cells was stimulated by fetal calf serum (FCS). This FCS-induced proliferation was not inhibited by cortisol. The CRH-induced ACTH secretion by corticotrophic adenoma cells was significantly (P < 0.05) lower than that by normal pituitary cells after 4 h incubation with CRH. Incubation with cortisol for 24 h resulted in reduced ACTH secretion under basal and AVP- or IGF-I-stimulated conditions. The relative inhibition was, however, significantly (P < 0.05) lower in ACTH-producing tumour cells than in normal pituitary cells. Cortisol did not inhibit the CRH-induced ACTH secretion in normal pituitary cells after 24 h. In conclusion, canine corticotrophic adenomas are less sensitive to stimulation by CRH and less sensitive to inhibition by glucocorticoids. These tumours have an aberrant sensitivity to a growth-promoting factor present in FCS. This factor may have an important role in the growth promotion of canine corticotrophic tumours.
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PMID:Effects of corticotrophin-releasing hormone, vasopressin and insulin-like growth factor-I on proliferation of and adrenocorticotrophic hormone secretion by canine corticotrophic adenoma cells in vitro. 953 96