UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteolytic cleavage of a G protein-coupled peptide hormone receptor, the renal V2 vasopressin receptor, by a plasma membrane proteinase was investigated. In the absence of protease inhibitors during incubation of bovine kidney membranes with a photoreactive vasopressin agonist, V2 receptor truncation leads to a labeled receptor fragment with M(r) 30,000. The V2 receptor-degrading enzyme could be completely inhibited by zinc ions yielding the native V2 receptor glycoprotein with M(r) 58,000. Studies with inhibitors of metalloendopeptidases involved in peptide hormone metabolism and with peptide substrates spanning the V2 receptor cleavage site classify the receptor protease as metalloendoproteinase with specificity for longer substrates. Comparison of the NH2-terminal protein sequence of the truncated M(r) 30,000 V2 receptor with the sequence deduced from the cDNA of the cloned bovine V2 receptor shows that cleavage occurs between Gln92 and Val93 of the second transmembrane helix close to an extracellular agonist binding site. V2 receptor proteolysis was dependent on the presence of a hormonal ligand. It occurred rapidly after hormone binding and led to a loss of ligand binding properties of the truncated V2 receptor. The data suggest that the endogenous V2 receptor-degrading metalloendoproteinase regulates V2 receptor function. The novel pathway may contribute to the termination of signal transmission.
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PMID:Ligand-induced cleavage of the V2 vasopressin receptor by a plasma membrane metalloproteinase. 789 81

The adult hypothalamo-neurohypophysial system, responsible for the secretion of the neurohormones, oxytocin, and vasopressin, undergoes reversible neuronal-glial and synaptic changes in response to stimulation (parturition, lactation, and osmotic stimulation). In the hypothalamus, these changes result in reduced astrocytic coverage of oxytocinergic somata and dendrites and concomitant increases in their GABAergic synapses; in the neurohypophysis, they lead to an enlarged neurovascular contact area. We discuss the possible role played by certain cell adhesion molecules, such as the highly sialylated isoform of the neural cell adhesion molecule, PSA-NCAM, the F3 glycoprotein, and the extracellular matrix molecule, tenascin, in such plasticity. The hypothalamo-neurohypophysial system continues to express high levels of these molecules during adulthood and they may serve as permissive factors to allow stimulus-induced structural remodelling to occur.
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PMID:Adhesion molecules and structural plasticity of the adult hypothalamo-neurohypophysial system. 793 46

High affinity binding sites for pancreastatin were identified for the first time, and their molecular characterization was performed with rat liver membranes. Using rat 125I-pancreastatin, we have studied the interaction of pancreastatin with liver membranes. Cross-linking of the tracer to the membranes was performed using the bifunctional reagent dithiobis(succinimidyl propionate). Analysis of binding under equilibrium conditions indicated the existence of one class of binding sites, with a Bmax of 15 fmol/mg of protein and an apparent Kd of 0.2 nM. The cross-linking of 125I-pancreastatin to liver membranes revealed a single band of M(r) 40,000, corresponding to the 125I-pancreastatin-receptor complex. The labeling of this complex was inhibited in the presence of rat pancreastatin (10(-10) to 10(-7) M) and in the presence of guanyl-5'-ylimidodiphosphate (10(-7) to 10(-4) M). Pretreatment of rat liver membranes with pertussis toxin did not affect pancreastatin binding or the inhibition by guanyl-5'-ylimidodiphosphate of pancreastatin binding. The specificity of pancreastatin binding was further assessed by displacement experiments with pancreastatin from other species and vasopressin. The binding of the pancreastatin-receptor complexes to Sepharose coupled to different lectins showed the glycoprotein nature of the pancreastatin receptor. These results strongly suggest that rat liver possesses a specific pancreastatin receptor, a glycoprotein of M(r) 35,000 that is coupled to a pertussis toxin-insensitive G protein in the plasma membrane.
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PMID:Receptors for pancreastatin in rat liver membranes: molecular identification and characterization by covalent cross-linking. 805 54

The renal glycoprotein hormone erythropoietin (Epo) is the key element in the feedback control of the production of red blood cells (RBC) in bone marrow. Excess of antidiuretic hormone (ADH) increases the RBC mass by increasing the synthesis of Epo. The mechanism of the Epo stimulating effect of ADH is not fully understood. Rats were treated with ADH with or without prior injection of a V1a-receptor antagonist. Additional experiments were carried out by stimulating the V2-receptor by desmopressin (DDAVP). Epo level in plasma was doubled following injections of ADH. Blockade of the V1a-receptor completely abolished the Epo stimulating effect of ADH. Neither ADH alone nor the combined giving of V1a-antagonist and ADH had an influence on the glomerular filtration rate or the renal plasma flow. Therefore, the increased Epo synthesis after application of ADH cannot be explained by a constriction of renal blood vessels with consecutive ischemic hypoxia. There is rather a direct stimulation of Epo synthesis by ADH via its receptors. Since a selective stimulation of the V2-receptor by DDAVP did not increase to Epo level in plasma, the observed increase of Epo is mediated by the V1a-receptor.
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PMID:Increased production of erythropoietin after application of antidiuretic hormone. A consequence of renal vasoconstriction? 853 59

This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.
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PMID:Water transport across mammalian cell membranes. 877 26

We studied the effect of glycoprotein GPIIb/IIIa (integrin alpha IIb beta 3) receptor occupancy by adenosine 5',1-thiotriphosphate (ATP alpha S), a competitive inhibitor of the ADP receptor, by fibrinogen, and by peptides containing the RGD (Arg-Gly-Asp) sequence as RGDW (Arg-Gly-Asp-Trp), RGDS (Arg-Gly-Asp-Ser), or the negative control RGGW (Arg-Gly-Gly-Trp) on human platelet physiological functions: aggregation, ATP secretion, and [Ca2+]in. As the presence of a nucleotide binding site on GPIIb alpha has been demonstrated in platelets [N. J. Greco, N. Yamamoto, B. W. Jackson, N. N. Tandon, M. Moos, and G. A. Jamieson (1991) J. Biol. Chem. 266, 13627-13633], we studied the effect of ATP alpha S, which specifically binds to this site, on platelet activation. We observed that ATP alpha S inhibited aggregation by thrombin, ADP, PMA, and ionophore A23187. Moreover, ATP alpha S dose dependently inhibited ATP secretion by ionophore A23187 and Ca2+ transients by thrombin and vasopressin in both the presence and absence of external Ca2+. Fibrinogen, although induced by a potentiation of platelet aggregation, inhibited ATP secretion and [Ca2+]in elevation induced by low thrombin concentrations or by vasopressin, interfering with both Ca2+ entry and Ca2+ release by the intracellular stores. RGD peptides, which specifically bind to GPIIb/IIIa, inhibited aggregation, secretion, and Ca2+ transients by thrombin, whereas the negative control RGGW did not exert any effect. We conclude that the occupancy of the GPIIb/IIIa receptor binding sites modulates platelet function by giving an inhibitory outside-in signal in platelets, particularly effective in platelets stimulated with low agonist doses. We suggest that ATP alpha S, fibrinogen, or RGD compounds, by interacting with GPIIb/IIIa receptor, prime some intracellular negative feedback mechanisms, which prevent further activation of circulating platelets by low-intensity stimuli and intravascular aggregation.
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PMID:Human platelet activation is inhibited by the occupancy of glycoprotein IIb/IIIa receptor. 880 80

Chromogranin A (CGA) is a calcium-binding glycoprotein thought to be the precursor of several peptides with defined biological activity. Chromogranin A has been localized in most endocrine cells and many neurons in the CNS. Here we studied its expression in neurons of the hypothalamo-neurohypophysial system, which secrete the neurohormones oxytocin and vasopressin. Light and electron microscopic immunocytochemistry and immunoblot analysis with antibodies specific for CGA revealed high levels of chromogranin A immunoreactivity throughout the hypothalamo-neurohypophysial system. In the supraoptic and paraventricular nuclei, it was characterized by intracytoplasmic labelling of magnocellular somata and processes and of certain astrocytes. Extensive labelling of fibres and dilatations characterized the internal layer of the median eminence and the neurohypophysis, transit and terminal site of the neurosecretory axons, respectively. Tanycyte-like cells in the median eminence also displayed reaction. Simultaneous immunofluorescence showed that oxytocinergic and vaso-pressinergic neurons contain chromogranin A. Electron microscopy revealed that chromogranin A immunoreactivity (visualized by pre-embedding immunoperoxidase or silver-enhanced colloidal gold techniques) was associated with neuro-secretory granules in hypothalamo-neurohypophysial system neurons. In astrocytes and pituicytes, it was seen over the cytoplasm and glial filaments. In tissue from colchicine-treated or immobilization-stressed rats, it was clear that chromogranin A immunoreactivity in the hypothalamus was confined to the hypothalamo-neurohypophysial system. In rats in which neurohypophysial secretion was strongly stimulated by dehydration, immunocytochemistry showed that hypothalamo-neurohypophysial system immunoreactivity significantly increased in the magnocellular nuclei but decreased in the neurohypophysis. On the other hand, chromogranin A distribution was not markedly affected by stress or lactation. These observations demonstrate that chromogranin A is present in neurons and, to a lesser degree, glial cells of the hypothalamo-neurohypophysial system and that its expression is closely related to that of the neurohypophysial peptides.
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PMID:Immunocytochemical localization of chromogranin A in the normal and stimulated hypothalamo-neurohypophysial system of the rat. 886 41

F3, a glycoprotein of the immunoglobulin superfamily implicated in axonal growth, occurs in oxytocin (OT)-secreting and vasopressin (AVP)-secreting neurons of the adult hypothalamo-neurohypophysial system (HNS) whose axons undergo morphological changes in response to stimulation. Immunocytochemistry and immunoblot analysis showed that during basal conditions of HNS secretion, there are higher levels of this glycosylphosphatidyl inositol-anchored protein in the neurohypophysis, where their axons terminate, than in the hypothalamic nuclei containing their somata. Physiological stimulation (lactation, osmotic challenge) reversed this pattern and resulted in upregulation of F3 expression, paralleling that of OT and AVP under these conditions. In situ hybridization revealed that F3 expression in the hypothalamus is restricted to its magnocellular neurons and demonstrated a more than threefold increase in F3 mRNA levels in response to stimulation. Confocal and electron microscopy localized F3 in secretory granules in all neuronal compartments, a localization confirmed by detection of F3 immunoreactivity in granule-enriched fractions obtained by sucrose density gradient fractionation of rat neurohypophyses. F3 was not visible on any cell surface in the magnocellular nuclei. In contrast, in the neurohypophysis, it was present not only in secretory granules but also on the surface of axon terminals and glia and in extracellular spaces. Taken together, our observations reveal that the cell adhesion glycoprotein F3 is colocalized with neurohypophysial peptides in secretory granules. It follows, therefore, the regulated pathway of secretion in HNS neurons to be released by exocytosis at their axon terminals in the neurohypophysis, where it may intervene in activity-dependent structural axonal plasticity.
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PMID:Regulated expression of the cell adhesion glycoprotein F3 in adult hypothalamic magnocellular neurons. 965 Dec 16

The arginine vasopressin (AVP) precursor gene of mammals contains three exons encoding the principal domains of the polyprotein precursor, including vasopressin (exon A), neurophysin (exon B), and glycopeptide (exon C). The AVP precursor (preprohormone) is processed and transported through the endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles, and finally, mature AVP is secreted from the posterior pituitary into the circulation. The exact steps of these processes during AVP translation and posttranslation events are not yet well elucidated. Defects in peptide processing are associated with several genetic disorders, including central diabetes insipidus (CDI). In the Brattleboro rat with CDI, the mRNA and protein of AVP are present in the hypothalamus, but no circulating AVP is detectable, thus suggesting a processing defect, transport defect, or both. The mutated AVP gene precursor of Brattleboro rat has a deletion of a single base, guanine, in the neurophysin coding region that leads to a frameshift resulting in the loss of the normal stop codon. It has been reported that the mutated precursor is trapped in the ER and does not reach the Golgi apparatus. Recent studies examined AVP secretion in cultured COS cells transfected with various constructs from wild-type and mutated Brattleboro AVP gene precursors. The wild-type in vitro studies demonstrated that intact neurophysin, but not the glycoprotein coding region, is necessary for normal AVP processing and secretion. Next, the results demonstrated that the guanine defect in the neurophysin coding region and the prolonged C-terminus accounted for the processing defect in the Brattleboro rat with CDI. These defects no doubt impair the folding and configuration necessary for normal processing of the AVP gene precursor in the ER. In hereditary CDI in humans, the majority of the mutations have also been shown to occur in the neurophysin coding region. However, in contrast to the recessive defect in the Brattleboro rat, in human CDI, neurotoxicity and denigration of the magnocellular neurons have been observed, and dominant inheritance occurs. Moreover, all mutations are missense, nonsense, or deletions in human CDI rather than the shift in reading frame and preserved neurons that is observed with the Brattleboro rat. Thus, the results from studies in the Brattleboro rat may only be partially applicable to hereditary CDI in humans.
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PMID:Vasopressin processing defects in the Brattleboro rat: implications for hereditary central diabetes insipidus in humans? 975 87

The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the presence of sex differences in the vasopressinergic and oxytocinergic systems. The present study was aimed at determining whether the sizes of AVP and OT neurons in the human SON and PVN show sex differences, as earlier studies demonstrated that a change in neuronal size is a sensitive parameter for activity. The minimal and maximal diameters were determined to estimate the volumes of cell somata and cell nuclei in AVP and OT neurons stained with an antibody against human glycoprotein-(22-39), a part of the AVP precursor, and a monoclonal anti-OT antibody in 15 men and 17 women ranging in age from 29-94 yr. The AVP neurons appeared to be larger in young men than in young women (< or =50 yr old). In elderly women (>50 yr old) AVP cell size considerably exceeded that in young women. In elderly men AVP neurons were larger than in young men and elderly women, although these differences were not significant. In addition, AVP cell size correlated positively with age in women but not in men. No significant differences were found in the AVP cell nucleus volumes among all four groups studied. Sex differences in the size of the PVN vasopressin neurons were pronounced at the left side (P = 0.048) and absent at the right side (P = 0.368), indicating the presence of functional lateralization in this nucleus. No difference was found in any morphometric parameter of OT neurons in the PVN among the 4 groups studied. Thus, our data demonstrate sex differences in the size of the AVP neurons, and thus in their function, that are age and probably also side dependent and the absence of such changes in OT neurons in the PVN. These data provide a basis for the reported higher AVP plasma levels in men compared to women.
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PMID:Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex. 1059 31

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