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)

Prior incubation of quiescent cultures of Swiss 3T3 cells with vasopressin leads to loss of mitogenic stimulation on its subsequent addition in the presence of a synergistic growth factor. This desensitization is selective for vasopressin, requires prolonged incubation (half-maximal desensitization after 12 hr of treatment) for its induction, and is reversed after a 48-hr incubation in the absence of vasopressin. It is elicited by concentrations of vasopressin, and several analogues, similar to those required for stimulation of DNA synthesis. Inhibition of 125I-labeled epidermal growth factor binding and stimulation of 86Rb+ uptake by vasopressin are also selectively decreased in the refractory cells. The vasopressin receptors that mediate mitogenesis in Swiss 3T3 cells are of the pressor type, not coupled to adenylate cyclase. These cells bind [3H]vasopressin in a specific and saturable (Kd = 1 X 10(-8) M) manner. The receptors are down-regulated after prolonged vasopressin treatment; however, this cannot provide a complete explanation of desensitization because cells that are completely refractory to vasopressin retain 60% of their [3H]vasopressin binding sites. Vasopressin refractoriness must therefore occur partly at a post-receptor locus.
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PMID:Vasopressin induces selective desensitization of its mitogenic response in Swiss 3T3 cells. 630 Aug 80

Prolonged treatment of Swiss 3T3 cells with phorbol 12,13 dibutyrate (PDB) rendered the cells refractory to subsequent mitogenic stimulation by both PDB and vasopressin. In contrast, the cells retained full responsiveness to a wide variety of other mitogens. An early response to vasopressin and phorbol esters, inhibition of (125I)-labeled epidermal growth factor [(125I)-EGF] binding, was also substantially decreased in PDB pretreated cells. The cross desensitization was not produced by vasopressin; this ligand induced homologous but not heterologous desensitization. Exposure of Swiss 3T3 cells to PDB caused a down regulation of (3H)-PDB receptors but did not reduce the binding of vasopressin to refractory cells. The time-course (t1/2 = 7 h) and dependence on PDB concentration (half maximal at 20 nM) for this phorbol ester receptor loss paralleled the induction of the mitogenic desensitizations to both PDB and vasopressin. However, the time-course of recovery revealed an important dissociation between receptor presence and mitogenic response. When Swiss 3T3 cultures, which had been pretreated with PDB, were washed to remove this ligand and incubated in its absence for 24 h, both (3H)-PDB receptors and PDB or vasopressin inhibition of (125I)-EGF binding were almost completely restored to control levels. However the homologous and heterologous mitogenic desensitizations showed a very different reversal time. After a 24-h recovery period PDB-treated refractory cells were still unable to synthesize DNA in response to PDB or vasopressin. The mitogenic desensitizations were however completely reversible; after a 48-h incubation in the absence of PDB the cells responded fully to the mitogenic actions of PDB or vasopressin. This finding suggests that a further postreceptor step was also desensitized by prolonged PDB treatment. The presence of a low level of cycloheximide during the PDB pretreatment blocked induction of this postreceptor refractoriness. We propose that this refractory postreceptor step selectively blocks both PDB and vasopressin stimulation of DNA synthesis and may represent the point at which the mitogenic pathways of phorbol esters and vasopressin converge.
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PMID:Homologous and heterologous mitogenic desensitization of Swiss 3T3 cells to phorbol esters and vasopressin: role of receptor and postreceptor steps. 631 36

Prior incubation of confluent, quiescent cultures of Swiss 3T3 cells with insulin leads to a selective loss of mitogenic stimulation on re-addition of the combination of vasopressin and insulin in serum-free medium. The desensitization is specific for the action of vasopressin as insulin is fully active in the refractory cells when added in combination with other mitogens, whereas vasopressin is not. A prolonged treatment with insulin is required for induction of the refractoriness, half-maximal loss of response occurs after about 7 h and desensitization is complete after 12 h treatment. The refractory cells recover their response to vasopressin after more than 24 h incubation in the absence of insulin. A rapid response of the cells to vasopressin, inhibition of 125I-epidermal growth factor (125I-EGF) binding, is also desensitized by insulin. Desensitization is induced by insulin-like growth factor I (IGF-I), and partially by desoctapeptide insulin, but not by insulin B chain. Although the characteristics of insulin-induced desensitization are very similar to those of the homologous desensitization induced by vasopressin treatment, insulin does not bind to vasopressin antiserum or the [3H]vasopressin receptors of Swiss 3T3 cells. Insulin treatment also does not lead to any down-regulation of [3H]vasopressin receptors, and the refractoriness of the cells must therefore lie at a post-receptor step. Both insulin- and vasopressin-induced refractoriness to the mitogenic action of vasopressin can be blocked by a low level of cycloheximide. Both these agents therefore seem to induce the synthesis of specific protein(s) which selectively inhibit the mitogenic response of the cell to vasopressin.
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PMID:Insulin induces a selective heterologous desensitization of the mitogenic response of Swiss 3T3 cells to vasopressin. 632

The growth factors FGF and vasopressin were found to have only a transient effect on confluent quiescent monolayers of Swiss 3T3 cells. Whether measured as cumulative entry into S-phase by autoradiography, or as cell division by time-lapse filming, the elevated rate of cell proliferation was maintained only over 10-15 hr. Several trivial or artifactual explanations for this transience were ruled out, including toxicity of 3H-thymidine; exhaustion or degradation of medium components, nutrients or growth factors (although some medium depletion was observed); and the generation during quiescence of cells incapable of division. We have also eliminated heritable variation in the capacity to respond to individual growth factors. However, unstable phenotypic heterogeneity in growth factor requirements between cells may play some part, as found elsewhere for the response to low concentrations of serum (Brooks et al, 1984). Cell populations that had ceased to respond to vasopressin recovered their sensitivity after 2-3 days' incubation in conditioned medium lacking vasopressin. The phenomenon thus resembles the mitogen-induced desensitization described by Collins and Rosengurt (1982, 1983). However, in our case, the loss of sensitivity was not selective for vasopressin but applied also to epidermal growth factor (EGF) and to prostaglandin F2 alpha. Furthermore, changes in responsiveness to vasopressin with time were associated with changes in cell density. Although some element of selective desensitization has not been ruled out, the transient response in our experiments can be accounted for in terms of unstable heterogeneity in growth factor requirements and/or in terms of density-dependent regulation of growth.
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PMID:Apparent desensitization of Swiss 3T3 cells to the mitogens FGF and vasopressin. 633 90

The effect of Lys-bradykinin on net Na+ influx in serum-deprived cultured human fibroblasts (HSWP cells) was measured. It was found that Lys-bradykinin stimulates net Na+ influx with a K1/2 of 1 nM. When Lys-bradykinin was combined with epidermal growth factor, vasopressin and insulin, the net Na+ influx stimulated was comparable with that measured in response to 10% serum. The above combination of growth factors also was found to stimulate DNA synthesis to 92% of the serum-stimulated levels in HSWP cells and to support cell growth over a period of 6 days. In addition, it was observed that the Na+ influx stimulated by Lys-bradykinin or by the combination of four growth factors was completely inhibited by the amiloride analog benzamil. Thus Lys-bradykinin presumably stimulates the same Na+ transport system as is stimulated by serum. Finally, the present results suggest that an increase in Na+ influx always accompanies DNA synthesis in HSWP cells. On the basis of these observations, it can be hypothesized that Na+ influx is a necessary event to stimulate DNA synthesis.
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PMID:Lys-bradykinin stimulates Na+ influx and DNA synthesis in cultured human fibroblasts. 633 76

Phosphatidylcholine (PC) biosynthesis in cultured 3T3 fibroblasts was increased in varying degrees by these mitogenic growth factors: fetal bovine serum, insulin, 12-O-tetradecanoylphorbol-13-acetate, epidermal growth factor, vasopressin, fibroblast growth factor and insulin-like growth factors I and II. PC synthesis was increased 2-4-fold by 10% serum, up to 4-fold by growth factors alone, and up to 8-fold by combinations of two or more growth factors. Single growth factors had no effect on the incorporation of [3H]choline into the acid-soluble precursors of PC, while serum or combinations of two or more mitogens could increase the incorporation of [3H]choline into acid-soluble material by up to 2-fold. Serum was shown to increase choline phosphorylation, choline kinase activity and the size of the phosphocholine pool. These data were utilized to calculate the radioactive specific activity of phosphocholine. Serum did not increase phosphocholine specific activity above control values; thus the increased incorporation of labelled choline into PC after serum stimulation resulted from increased PC synthesis and not from a simple change in specific activity of precursor phosphocholine.
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PMID:Regulation of phosphatidylcholine biosynthesis by mitogenic growth factors. 636 72

Quiescent 3T3 fibroblasts grown on microcarrier beads and loaded with the [Ca2+] indicator quin2 had a cytosolic free Ca2+ concentration ( [Ca2+]i) of 154 +/- 11 nM (SE; n = 32). Stimulation with the mitogens vasopressin, epidermal growth factor (EGF) or prostaglandin F2 alpha (PGF2 alpha) caused a very rapid increase in [Ca2+]i to a maximum of 200-500 nM after 60-90 s. [Ca2+]i declined thereafter to a level above that in quiescent cells which was maintained for at least 15 min. In contrast no immediate effects on [Ca2+]i were detected after the addition of the mitogens insulin or 12-O-tetradecanoylphorbol 13-acetate (TPA). These studies indicate that early changes in [Ca2+]i may be involved in the action on fibroblasts of some, but not all, mitogens.
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PMID:Some mitogens cause rapid increases in free calcium in fibroblasts. 637 Jul 23

Cystamine together with colchicine markedly enhanced the uptake of [3H]-thymidine into DNA of quiescent cultures of insulin-stimulated Swiss 3T3 mouse fibroblasts. Flow cytofluorometric analyses showed an increased rate of transition of cells from G0/G1----S + G2 in response to combinations of insulin, colchicine, and cystamine. Cystamine, the most effective of several thiol compounds, gave maximal augmentation at 200 microM and was toxic at 300-500 microM. Amplification of DNA synthesis by cystamine was also obtained with epidermal growth factor, vasopressin, and 0.5% fetal bovine serum. Combinations of cystamine and other microtubule-disrupting agents such as nocodazole, maytansine, and podophyllotoxin enhanced DNA synthesis in insulin-stimulated cells. In experiments involving sequential addition of agents, significant enhancement of DNA synthesis was observed when the addition of colchicine to cystamine-treated cells was delayed or conversely when the addition of cystamine to colchicine-treated cultures was delayed. This reciprocal interaction between cystamine and colchicine suggests that a prereplicative intermediate accumulates in response to the action of these dissimilar compounds. We consider the possibility that cystamine may act by forming mixed disulfides with thiol groups of unknown protein(s) that regulate DNA replication.
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PMID:Cystamine augments the stimulation of DNA synthesis by peptide growth factors and microtubule-disrupting agents in cultures of 3T3 mouse fibroblasts. 637 30

We discuss our recent findings in three related areas of the gene amplification field. 1) We have found that tumor-promoting phorbol esters, nonphorbol tumor promoters, and most significantly, mitogenic hormones, such as insulin, vasopressin, and epidermal growth factor (EGF), greatly increase the incidence of methotrexate (MTX) resistance in 3T6 cells under condition of MTX selection. Most of these MTX-resistant cells bear amplified dihydrofolate reductase (DHFR) genes. 2) We have discovered that when mouse cells bearing unstably amplified DHFR genes are grown in the presence of nonlethal concentrations of hydroxyurea (HU), the rate of loss of the DHFR genes from these cells is greatly increased. 3) We have developed a new method for detection and mapping of homologous, repeated and amplified DNA sequences, and have used this method to detect and clone amplified DNA fragments in mammalian cells resistant simultaneously to a number of different drugs.
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PMID:Acquisition and loss of amplified genes: dramatic effects of hormones, tumor promoters and cytotoxic drugs. 639 91

Rat liver cells (the C-9 cell line) are capable of producing, from endogenously liberated arachidonic acid, prostaglandins I2, E2 and F2 alpha. Greater than 95% of these cyclooxygenase products is prostaglandin I2. Arachidonic acid metabolism is stimulated by treatment of the C-9 cells with epidermal growth factor, vasopressin, angiotensin II or thrombin. Stimulation by combined treatments with vasopressin, angiotensin II or thrombin is additive; but each stimulation, when incubated in the presence of epidermal growth factor, is synergistic. These stimulations are dependent on Ca++. They are inhibited by indomethacin and dexamethasone. The cells exhibit homologous, but not heterologous, desensitization to vasopressin and thrombin. The synergistic stimulation by epidermal growth factor and vasopressin is inhibited by prior treatment of the cells with epidermal growth factor.
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PMID:Arachidonic acid metabolism by rat liver cells (the C-9 cell line). 643 71


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