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)

Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide receptors, and are reported to inhibit growth of small cell lung cancer cell lines (SCLC CLs). We found [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D-Phe5SP) significantly inhibited DNA synthesis by 10/10 human tumour CLs; six SCLC, one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma, with inhibition to 50% control levels (IC50) of 20-50 microM. There was dose dependent inhibition of colony forming efficiency (CFE) in 3/3 SCLC and 1/1 N-SCLC CL, IC50s of 0.5-6.5 microM in 5% serum. Exposure of SCLC CL HC12 to 100 microM D-Phe5SP for 1-4 h caused a progressive fall in viable cell number; surviving cells, grown in the absence of peptide, showed a decreased growth rate. During 1 week's exposure of two SCLC CLs to 20 microM D-Ph5SP, growth was slower than control cultures, while 50-100 microM completely inhibited growth. These inhibitory effects were partially reversed by increasing serum concentration from 5 to 20%, but not by SP, vasopressin, bombesin or insulin-like growth factor 1. There was some inhibition of CFE by 3/3 normal human bone marrows, IC50s of 30-80 microM, compared with 8 microM for HC12 in 20% FCS. Therefore D-Phe5SP appears to have more potent antiproliferative effects in tumour cells than normal cells, suggesting a role for this analogue in tumour treatment.
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PMID:In vitro effects of substance P analogue [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P on human tumour and normal cell growth. 137 71

Three main pathways have been implicated in desensitization of receptors that stimulate adenylylcyclase (AC): cAMP-mediated phosphorylation; cAMP-independent phosphorylation, and receptor internalization. Cell lines derived from the murine Ltk- cell were found useful in exploring the contribution of cAMP-dependent phosphorylation in V2 vasopressin receptor desensitization. The HTB-2 cell expresses the human V2 vasopressin receptor, introduced by transfection of human genomic DNA, and the prostaglandin E1 (PGE1) receptor, endogenous to the Ltk- cell. The A7 cell expresses the hamster beta 2-adrenoceptor, which undergoes the above-mentioned desensitization processes. Treatment of HTB-2 cells with arginine-vasopressin (AVP) had no effect on AC responsiveness to PGE1, but promoted desensitization of the AVP response. This was seen as a 5-6-fold right shift in the dose-response curves for AVP action (cAMP accumulation in intact cells and AC stimulation in homogenates and isolated membranes) and in a decrease in the maximum effect of AVP on these parameters. AVP treatment caused a decrease in cell surface receptors to approximately 75% of control without changes in KD, as determined by Scatchard analysis. When cAMP was increased by treatment with 10 microM PGE1 and isobutylmethylxanthine, desensitization of the PGE1 receptor was observed but not of the AVP receptor. In A7 cells the same treatment caused, as expected, a 3-fold right shift in the dose-response curve for AC stimulation by isoproterenol, indicating that L cells can mediate heterologous desensitization. These data demonstrate that the V2 vasopressin and the PGE1 receptors undergo homologous desensitization in the absence of cAMP-mediated phosphorylation and that this component is not required for vasopressin receptor internalization.
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PMID:Desensitization of the human V2 vasopressin receptor. Homologous effects in the absence of heterologous desensitization. 137 12

Molecular cloning of the vasotocin gene of a cyclostome, the Pacific hagfish Eptatretus stouti, reveals, in contrast to other known members of the vertebrate vasopressin/oxytocin hormone gene family, an unusual exon-intron organization. Although the location of three exons and two introns is conserved, an additional intron is present 5' of the coding region of the hagfish gene. The third intron, which is greater than 14 kilobase pairs in size, contains on the opposite DNA strand to that encoding vasotocin an open reading frame exhibiting striking similarity to the putative transposase of Tc1-like nonretroviral mobile genetic DNA elements, so far reported only from nematodes and Drosophila. The hagfish element, called Tes1, is flanked by inverted terminal repeats representing an example of the existence of a typical inverted terminal-repeat transposon within vertebrates. The presence of Tc1-like elements in nematodes, Drosophila, and cyclostomes indicates that these genetic elements have a much broader phylogenetic distribution than hitherto expected.
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PMID:Presence of a member of the Tc1-like transposon family from nematodes and Drosophila within the vasotocin gene of a primitive vertebrate, the Pacific hagfish Eptatretus stouti. 137 21

Recent progress in the molecular biological approach to analysis of inherited tubular transport abnormalities is reviewed. 1) cDNAs of several mammalian proteins, related to amino acid transport in renal tubular cell, have been cloned using an expression cloning in Xenopus oocytes. One of them stimulates the transport of cystine, dibasic amino acids and neutral amino acids and will accelerate the analysis of cystinuria. 2) Isolation of cDNAs, encoding human and rat vasopressin V2 receptors, has been reported. The deduced amino acid sequence seems to be a member of receptors with seven putative transmembrane regions. Analysis of this gene from patients with nephrogenic diabetes insipidus is in progress. 3) Analysis of carbonic anhydrase II (CA II) gene in a Belgian family with renal tubular acidosis associated with osteoporosis and cerebral calcification has shown a point mutation replacing an invariant histidine residue of CA II protein with tyrosine. 4) Oculocerebrorenal syndrome of Lowe (OCRL) is a X-linked disorder affecting the lens, brain and kidneys. The OCRL locus has been mapped to Xq24-26 by linkage analysis and by finding de novo X-autosome translocations at Xq24-26 in two unrelated females with OCRL. A cDNA has been isolated using yeast artificial chromosome and DNA inserts that span the X chromosome breakpoint from a female patient. Transcript for this cDNA is absent in unrelated male patients. The open reading frame encodes a new protein similar to human inositol-polyphosphate-5-phosphatase, raising a possibility that OCRL is an inborn error of inositol phosphate metabolism.
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PMID:[Recent progress in molecular biology of inherited tubular transport abnormalities]. 149 59

Antisense peptides, amino acid sequences encoded in the antisense strand of DNA, can interact with significant affinity and selectivity with their corresponding sensepeptides. Experimentally, sense-antisense peptide recognition has been observed repeatedly. However, skepticism about the biological relevance of this phenomenon has persisted. This is due in part to the unexpected and somewhat couterintutive nature of the interaction as well as to its non-universality as an empirical observation. Nonetheless, antisense peptides in several cases investigated so far have been used as immobilized ligands for the successful affinity chromatographic separation of native (sense) peptides and proteins. For example, immobilized antisense peptides corresponding to Arg8-vasopressin (AVP) have been used to separate vasopressin from oxytocin chromatographically as well as to affinity capture AVP-receptor complex. These results, together with improved understanding of the general features of amino acid sequence which drive antisense-sense peptide interactions as well as new ideas for making antisense peptides chimeras, are beginning to suggest improved ways to make antisense-related peptides as affinity agents for separation as well as for other biotechnology applications.
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PMID:Interactions and uses of antisense peptides in affinity technology. 151 30

Antidiuresis, the recovery of water from the lumen of the renal collecting tubule, is regulated by the hypothalamic release of antidiuretic hormone (ADH), which binds to specific receptors on renal collecting tubule cells, stimulates adenylyl cyclase and promotes the cyclic AMP-mediated incorporation of water pores into the luminal surface of these cells. We report here the isolation of the human ADH receptor gene using a genomic expression cloning approach. The gene was used to clone the complementary DNA from a human renal library. The deduced amino-acid sequence of the receptor yields a hydropathy profile characteristic of receptors with seven putative transmembrane regions. This and the comparison with other cloned receptors indicates that the ADH receptor is a member of the superfamily of G-protein-coupled receptors.
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PMID:Molecular cloning of the receptor for human antidiuretic hormone. 153 49

Human hepatocyte growth factor is a newly discovered substance that stimulates DNA synthesis in vitro. In this study, we examined intracellular Ca2+ movement as one of the second messengers for human hepatocyte growth factor in primary-cultured hepatocytes. The addition of hHGF induced Ca2+ oscillation, but the frequency of oscillations varied from cell to cell. We also saw marked intercellular heterogeneity in the initial latent period for the Ca2+ response; the mean latent period was rather longer than those seen with phenylephrine and vasopressin. This difference in the initial latent period may be due to the difference in the pathways of Ca2+ elevation. Duration of culture determined the number of human hepatocyte growth factor-responsive cells; their number peaked at 2 to 5 hours of confluent culture, whereas the peak was earlier in a low-density culture. These changes in responsiveness during culture can be explained by the cell cycle-dependent sensitivity to human hepatocyte growth factor of hepatocytes. The Ca2+ response to human hepatocyte growth factor was dose dependent; 10(-10) mol/L hHGF gave the highest Ca2+ response, similar to the dose-response curve of DNA synthesis. We even observed the Ca2+ response in the Ca(2+)-free buffer, so the increase in Ca2+ was considered due to release from intracellular Ca2+ stores. These results suggest that human hepatocyte growth factor causes the intracellular Ca2+ elevation in the early stage of the cell cycle and that it plays important roles in the signal transduction systems for human hepatocyte growth factor and the proliferation of hepatocytes.
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PMID:Intracellular calcium as a second messenger for human hepatocyte growth factor in hepatocytes. 153 8

The hepatic, vascular-type (V1aR) and the renal, antidiuretic-type (V2R) vasopressin receptor cDNAs were recently cloned from rat liver and kidney libraries, respectively. DNA fragments containing the region encoding the putative 5/6 transmembrane loops of these receptors were subcloned, separately, into RNA polymerase promoter-containing vectors from which 35S-labeled sense and antisense riboprobes were synthesized. In situ hybridization histochemistry showed high levels of V1aR transcripts in the liver and the renal medulla among the vascular bundles. Sparser labeling was found in the renal cortex, but there were no grains over the glomeruli. V1aR mRNA was detected in many brain areas, including the hippocampal formation, central amygdala, dorsolateral septum, lateral hypothalamus, suprachiasmatic, ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus, nucleus of the solitary tract, cerebellum, spinal nucleus of the trigeminal tract, reticular formation, inferior olivary nucleus, and choroid plexus. Rare labeled cells were seen along the periphery of the posterior pituitary. V2R transcripts were not detected in the liver or brain, but were present in high amounts in the inner and outer renal medulla, primarily associated with collecting ducts. Sparser labeling was found in the renal cortex, and no grains were seen over the glomeruli. These data confirm the expression of the V1a vasopressin receptor in liver and brain and demonstrate that kidney expresses mRNAs encoding V1a and V2 vasopressin receptors.
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PMID:Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in rat liver, kidney, pituitary and brain. 153 12

The neurohypophyseal hormone arginine vasopressin has diverse actions, including the inhibition of diuresis, contraction of smooth muscle, stimulation of liver glycogenolysis and modulation of adrenocorticotropic hormone release from the pituitary. Arginine vasopressin receptors are G protein-coupled and have been divided into at least three types; the V1a (vascular/hepatic) and V1b (anterior pituitary) receptors which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+, and the V2 (kidney) receptor which is coupled to adenylate cyclase. We report here the cloning of a complementary DNA encoding the hepatic V1a arginine vasopressin receptor. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA corresponding to the cDNA is distributed in rat tissues known to contain V1a receptors.
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PMID:Molecular cloning and expression of a rat V1a arginine vasopressin receptor. 156 Aug 25

Four temperature-sensitive cell-cycle mutants of rat 3Y1 clonal fibroblasts representing separate complementation groups (3Y1tsD123, 3Y1tsF121, 3Y1tsG125 and 3Y1tsH203) are arrested at restrictive temperature, primarily with a G1-phase DNA content (temperature arrest). We examined various factors affecting signal transduction for activity which induces DNA synthesis at the restrictive temperature when added to the temperature-arrested cultures of these mutants. The factors examined were theophylline, dibutyryl cyclic AMP, cholera toxin (CT), dibutyryl cyclic GMP, sodium nitroprusside, phorbol 12-myristate 13-acetate, 1-oleoyl 2-acetylglycerol, bombesin, vasopressin, basic fibroblast growth factor (FGF), platelet-derived growth factor, A23187, monensin, epidermal growth factor (EGF), insulin and fetal calf serum (FCS). None of these factors induced DNA synthesis in 3Y1tsH203. In one mutant (3Y1ts121), FGF, EGF and FCS individually induced DNA synthesis. In the other 2 mutants (3Y1tsD123 and 3Y1tsG125), FGF and CT individually induced DNA synthesis. The FGF-induced DNA synthesis was suppressed by islet-activating protein (IAP) in 3Y1tsD123 and 3Y1tsG125, but not in 3Y1tsF121. The CT-induced DNA synthesis was also suppressed by IAP, as previously shown. When temperature-arrested cultures were shifted to a permissive temperature, all 4 mutants initiated DNA synthesis in the presence of IAP. These results suggest that (1) a cell can prepare for the initiation of DNA synthesis by using several independent signal transduction pathways, and (2) in a given situation, the cell uses a particular pathway because of its availability, which depends on the culture conditions.
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PMID:Induction of DNA synthesis by fibroblast growth factor in temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts arrested at restrictive temperature. 158 64


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