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)

Quiescent Swiss 3T3 cells can be stimulated to reenter the cell cycle by various mitogens used in synergistic combinations with insulin-like growth factors (IGFs). The cells constitutively secrete an IGF-binding protein (IGFBP), which can modulate the interaction of IGFs with their receptors and could, therefore, alter cellular responsiveness to IGFs. We have now characterized the IGFBP secreted by Swiss 3T3 cells and tested whether its secretion is regulated by heterologous mitogens. Ligand blotting using [125I]IGF-I revealed a major IGFBP of 40,000 mol wt, and treatment of the cells with tunicamycin reduced the mol wt of this protein to about 32,000. mRNA from Swiss 3T3 cells hybridized to a 32P-labeled oligonucleotide (50-mer) complementary to rat IGFBP-3. Taken together, these results indicate that the principal IGFBP secreted by Swiss 3T3 cells is probably the N-glycosylated IGFBP-3. Production of this IGFBP by Swiss 3T3 cells was stimulated by 50-150% by the mitogens bombesin, vasopressin, platelet-derived growth factor, epidermal growth factor, and 12-O-tetradecanoylphorbol 13-acetate and also by IGF-I. The increased production of IGFBP was first detected after 4-6h of incubation and was then maintained for 48-72 h. Agents that elevate intracellular cAMP and the glucocorticoid dexamethasone reduced IGFBP output. In cells in which protein kinase-C had been down-modulated, the stimulation of IGFBP output by 12-O-tetradecanoylphorbol 13-acetate was abolished, but the stimulation induced by the other mitogens was not prevented. Thus, the production of IGFBP by Swiss 3T3 cells can be regulated by a number of different signalling pathways.
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PMID:Mitogens regulate the production of insulin-like growth factor-binding protein by Swiss 3T3 cells. 170 79

The author presents an account of selected important findings in endocrinology during the last year. The mediator of action of STH, IGF-I, was tested as a protein anabolic in a child with Laron's nanism. STH is about to be tested as a geriatric drug. A non-peptide vasopressin antagonist was described. Melatonin is being tested in sleep disorders. A combination of methimazol and thyroxine is more suitable for treatment of Graves-Basedow's disease than the goitrogen alone. Dermal vasoconstriction can be an indicator of the effectiveness of glucocorticoids in asthma. Significant advances were made in the sphere of the new hormone, NO: it is not only an effective vasorelaxing agent but also a neuromodulator and participates in the natural lymphocytic cytotoxicity. Marked advances were made as regards knowledge of the endogenous ligand for benzodiazepine receptors.
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PMID:[Endocrinology 1990-1991]. 180 40

Fetal brown adipocyte primary cultures increase DNA synthesis; cell number; and DNA, RNA, and protein contents in response to 10% fetal calf serum, IGF-I, and EGF plus vasopressin plus bombesin when added for 64 h to quiescent cells. IGF-I is a complete growth factor in this system while EGF needs the presence of vasopressin plus bombesin for its maximal proliferative effects. These mitogens induce the genetic expression of G6P dehydrogenase, increasing its mRNA content as well as its specific activity and amount of immunoreactive protein. The presence of cAMP elevating agents prevents the stimulatory effect of EGF plus vasopressin plus bombesin on DNA synthesis, cell number, and DNA content as well as on the induction of G6P dehydrogenase expression. Thus, changes on the proliferative state of these cells are associated with the level of expression of G6P dehydrogenase.
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PMID:Proliferation of fetal brown adipocyte primary cultures: relationship with the genetic expression of glucose 6 phosphate dehydrogenase. 202 77

We have characterized a plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and a cytosolic phosphatidylinositol (PI)-specific PLC in human liver. Epinephrine, 1 x 10(-5) M, and vasopressin, 1 x 10(-8) M, stimulated PIP2-PLC which was enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). PI-PLC stimulation was not observed by these agents. Insulin and insulin-like growth factors (IGF-I and IGF-II) in the presence and absence of GTP gamma S did not stimulate PIP2-PLC or PI-PLC in plasma membranes and cytosol preparations nor phosphoinositide breakdown in isolated human hepatocytes. Furthermore, serendipitly we found that PIP2-PLC activity was increased in liver membranes from obese patients with type II diabetes when compared to obese and lean controls. We conclude that in human liver, insulin and IGFs are not members of the family of hormones generating inositol trisphosphate (IP3) as a second messenger. Furthermore, the increased PIP2-PLC in diabetic liver may result in: (a) increased intracellular concentrations of IP3 and thus increased Ca2+, which has been postulated to induce insulin resistance; and (b) increased diacylglycerol and thus increased protein kinase C which phosphorylates the insulin receptor at serine residues inactivating the insulin receptor kinase. While the mechanism of increased PIP2-PLC activity in diabetes is unknown, it may initiate a cascade of events that result in insulin resistance.
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PMID:Effect of insulin and insulin-like growth factors I and II on phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate breakdown in liver from humans with and without type II diabetes. 254 Jan 78

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 situ hybridization was used to map cellular patterns of gene expression for facilitative glucose transporters (GTs) 1-5 in the developing and adult rat kidney. GT3 was not detected. GT1 mRNA was present in the proximal straight tubule (PST), distal nephron and collecting duct. GT2 mRNA was localized in both proximal convoluted and PST, while GT5 mRNA was detected only in the PST. GT4 mRNA and immunoreactivity were focally localized in the thick ascending limb of Henle's loop and were coexpressed with IGF-I. Thus, each of the four different isoforms demonstrated a distinct renal distribution, with GTs 1, 2, and 5 coexpressed in the PST. Renal GT1 and GT5 gene expression were unchanged throughout development, while GT2 was most abundant before weaning and GT4 was first detected after weaning. Only GT4 appeared to be hormonally regulated: It was decreased after hypophysectomy and increased after vasopressin treatment, but was not affected by 1 or 4 d of insulinopenic diabetes mellitus. The coexpression of GT4 and IGF-I in the thick ascending limb segment of the nephron suggests a novel autocrine/paracrine mechanism by which cells may control local fuel economy independently from that of the larger structure to which they belong and from the systemic hormonal milieu.
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PMID:Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney. 847 19

Terminal differentiation of myogenic cells has long been known to be positively regulated by insulin-like growth factors (IGFs). Arg8-vasopressin (AVP) has been recently reported to potently induce myogenic differentiation. In the present study, the effects and the mechanisms of action of AVP and IGFs on myogenic cells have been investigated under conditions allowing growth and differentiation of myogenic cells in a simple serum-free medium. Under these conditions, L6 and L5 myogenic cells slowly proliferate and do not undergo differentiation (less than 1% fusion up to 7 days). AVP rapidly (2-3 days) and dose-dependently induces the formation of multinucleated myotubes. Creatine kinase activity and myosin accumulation are strongly up-regulated by AVP. Insulin or IGF-I or IGF-II, at concentrations that cause extensive differentiation in serum-containing medium, induces a modest degree of differentiation in serum-free medium. The simultaneous presence of AVP and of one of the IGFs in the synthetic medium induces maximal differentiation of L6, L5, and satellite cells. The expression of both myogenin and Myf-5 is dramatically stimulated by AVP. Our results indicate that AVP induces a significant level of myogenic differentiation in the absence of other factors. Furthermore, they suggest that to express their full myogenic potential, IGFs require the presence of other factors normally present in serum and fully mimicked by AVP. These studies support the conclusion that terminal myogenic differentiation may depend on the presence of differentiation factors rather than the absence of growth factors.
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PMID:Vasopressin and insulin-like growth factors synergistically induce myogenesis in serum-free medium. 948 52

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 neurohypophyseal nonapeptide Arg8 vasopressin (AVP) promotes differentiation of cultured L6 and L5 myogenic cell lines and mouse primary satellite cells. Here, we investigated the molecular mechanism involved in the induction of the myogenic program by AVP. In L6 cells, AVP treatment rapidly induces Myf-5, myogenin, and myocyte enhancer factor 2 (MEF2) mRNAs, without affecting the expression of known myogenic growth factors such as IGF-I, IGF-II, or their receptors. In the presence of cycloheximide, AVP up-regulates the expression of MEF2, but not of myogenin, indicating that the synthesis of a protein intermediate is not necessary for MEF2 induction. Notably, AVP treatment activates a calcium/calmodulin kinase signaling pathway that induces cytosolic compartmentalization of the histone deacetylase 4, a mechanism related to the transcriptional activation of MEF2. The activity of chloramphenicol acetyltransferase reporter constructs carrying the Myo184 and Myo84 fragments of the myogenin promoter is also induced by AVP. Mutation of the MEF2 site completely abolishes the response to AVP, whereas deletion of the E1 site present in pMyo84 does not impair this response. Together, these results show that AVP induces myogenic differentiation through the transcriptional activation of MEF2, a mechanism that is critical for myogenesis.
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PMID:AVP induces myogenesis through the transcriptional activation of the myocyte enhancer factor 2. 1204 25

We evaluated the GH-releasing effect of GHRH plus arginine (ARG) in 36 patients (22 males and 14 females) with acquired GH deficiency including idiopathic inflammatory pituitary stalk thickness (n = 15), Langerhans cell histiocytosis (LCH) affecting the hypothalamic-pituitary area (n = 11), and craniopharyngioma (n = 10). All of the patients (mean age, 9.6 +/- 3.1 yr; range, 5.6-20.8) showed GH response less than 10 microg/liter after 2 pharmacological stimuli and were tested with GHRH plus ARG at a mean age of 11.2 +/- 4.1 yr. Twenty-nine patients had vasopressin deficiency, 10 had TSH deficiency, 8 had gonadotropin deficiency, and 4 had ACTH deficiency. The median peak GH response to insulin test was 2.1 microg/liter (range, 1.1-2.9), whereas it was 1.5 microg/liter (range, 1.3-2.4) after ARG. The median peak GH response to insulin was significantly lower in the patients with craniopharyngioma (1.4 microg/liter; range, 0.8-1.7) than in the patients with idiopathic pituitary stalk thickness (2.2 microg/liter; range, 1.0-2.4) or with LCH (2.6 microg/liter; range 2.0-4.3, P = 0.02). The median peak GH response to ARG was significantly lower in the patients with idiopathic inflammatory pituitary stalk thickness (1.3 microg/liter; range, 0.8-1.8) than in those with craniopharyngioma (1.5 microg/liter; range, 1.1-1.6) or with LCH (2.8 microg/liter; range, 1.9-3.2, P = 0.00007). The median peak GH response after GHRH plus ARG was significantly lower in the overall patient population (8.3 microg/liter; range, 4.4-28.4) than in the age-matched controls (49.8 microg/liter; range, 39.9-81.6, P < 0.00001). The median peak GH response was significantly lower in the patients with craniopharyngioma (4.6 microg/liter; range, 3.6-6.3) than in those with LCH (8.9 microg/liter; range, 4.4-28.4) or with idiopathic pituitary stalk thickness (12.6 microg/liter, range, 6.4-24, P = 0.07). Ten patients had a GH response of more than 20 microg/liter after GHRH plus ARG. There was a trend toward a decrease in peak GH response to GHRH plus ARG (r = -0.57, P = 0.06) as patient age increased. For cut-off values of 20 microg/liter, the sensitivity of GHRH plus ARG was 75% (95% CI, 57.8-87.9%) and the specificity was 96.4% (95% CI, 89.9-99.2%); whereas, for cut-off values of 24.2 microg/liter, sensitivity was 86.1% (95% CI, 70.5-95.3%), and specificity was 95.2% (95% CI, 88.2-98.7%). The median IGF-I level did not differ between the children with idiopathic pituitary stalk thickness (57 microg/liter; range, 46-68), those with LCH (55 microg/liter; range, 34-63), and those with craniopharyngioma (41 microg/liter; range, 39-49). The present study confirmed the diagnostic potential of the GHRH-plus-ARG test in children with acquired GH deficiency caused by hypothalamic-pituitary lesion. It stimulates GH secretion to a greater extent in those patients with GH deficiency with primary involvement of the hypothalamic area, e.g. patients with idiopathic pituitary stalk thickness or LCH, than in those with both hypothalamic and pituitary lesion, as in craniopharyngioma. In some patients, the GHRH-plus-ARG test stimulates GH response to a so-called: normal value, suggesting that pituitary responsiveness to GHRH plus ARG may fail to recognize acquired GHD. Finally, the number of pituitary hormone deficits and the patient's age affect the GH response to GHRH plus ARG.
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PMID:GHRH plus arginine in the diagnosis of acquired GH deficiency of childhood-onset. 1205 Feb 43


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