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)

Nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine in response to vasopressin. The autosomal recessive form of NDI is caused by mutations in the AQP2 gene, encoding the vasopressin-regulated water channel of the kidney collecting duct. This report presents three new mutations in the AQP2 gene that cause NDI, resulting in A147T-, T126M-, or N68S-substituted AQP2 proteins. Expression of the A147T and T126M mutant AQP2 proteins in Xenopus oocytes revealed a relatively small, but significant increase in water permeability, whereas the water permeability of N68S expressing oocytes was not increased. cRNA encoding missense and wild-type AQP2 were equally stable in oocytes. Immunoblots of oocyte lysates showed that only the A147T mutant protein was less stable than wild-type AQP2. The mutant AQP2 proteins showed, in addition to the wild-type 29-kd band, an endoplasmic reticulum-retarded form of AQP2 of approximately 32 kd. Immunoblotting and immunocytochemistry demonstrated only intense labeling of the plasma membranes of oocytes expressing wild-type AQP2. In summary, two mutant AQP2 proteins encoded in NDI are functional water channels. Therefore, the major cause underlying autosomal recessive NDI is the misrouting of AQP2 mutant proteins.
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PMID:New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels. 904 43

Transcripts encoding the vasopressin precursor are located in axons and dendrites of rat hypothalamic magnocellular neurons. While the axonal vasopressin mRNA has been extensively characterized both at the biochemical and morphological level, little is known about those transcripts residing in dendrites of magnocellular neurons. As revealed by in situ hybridization at the electron microscopic level, the mRNA is located in proximal and distal dendritic segments and is exclusively confined to regions containing rough endoplasmic reticulum. These results suggest that dendrites of hypothalamic neurons may be capable of local precursor synthesis independent of that occurring in the cell somata. A heterologous system has been employed to define cis-acting elements within the vasopressin mRNA which may be involved in dendritic compartmentalization. Expression vector constructs consisting of the cytomegalovirus promoter coupled to the rat vasopressin cDNA have been injected into the cell nuclei of cultured neurons derived from embryonic rat superior cervical ganglia. Vector-encoded vasopressin transcripts were also sorted to dendrites of these neurons indicating that the molecular determinants of dendritic mRNA transport are not cell specific. Mapping of the targeting elements revealed two segments within the vasopressin mRNA that are able to confer dendritic compartmentalization to alpha-tubulin mRNA which is normally confined to the cell body.
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PMID:Dendritic localization of rat vasopressin mRNA: ultrastructural analysis and mapping of targeting elements. 910 94

Mutations in the arginine vasopressin (AVP) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (FNDI). The dominant inheritance pattern has been postulated to reflect neuronal toxicity of the mutant proteins, but the mechanism for such cytotoxicity is unknown. In this study, wild-type or several different mutant AVP genes were stably expressed in neuro2A neuroblastoma cells. When cells were treated with valproic acid to induce neuronal differentiation, each of the mutants caused reduced viability. Metabolic labeling revealed diminished intracellular trafficking of mutant AVP precursors and confirmed inefficient secretion of immunoreactive AVP. Immunofluorescence studies demonstrated marked accumulation of mutant AVP precursors within the endoplasmic reticulum. These studies suggest that the cellular toxicity in FNDI may be caused by the intracellular accumulation of mutant precursor proteins.
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PMID:Molecular basis of autosomal dominant neurohypophyseal diabetes insipidus. Cellular toxicity caused by the accumulation of mutant vasopressin precursors within the endoplasmic reticulum. 910 34

Function and biochemical properties of the V2 vasopressin receptor (V2R) mutant R337ter, identified in patients suffering from X-linked recessive nephrogenic diabetes insipidus, were investigated by expression in COS.M6 or HEK293 cells. Binding assays and measurements of adenylyl cyclase activity failed to detect function for the truncated receptor, although metabolic labeling demonstrated normal levels of protein synthesis. ELISA assays performed on cells expressing the receptors tagged at the amino terminus with the HA epitope failed to detect V2R R337ter on the plasma membrane. Treatment with endoglycosidase H revealed that the receptor was present only as a precursor form because the mature R337ter V2R, resistant to endoglycosidase H treatment, was not detected. The precursor of V2R-R337ter had a longer half-life than that of the wild type V2R, suggesting that arrested maturation may slow the degradation of the precursor. Unrelated experiments had demonstrated that V2R-G345ter, containing eight additional amino acids, was expressed on the plasma membrane and functioned normally. Receptor truncations longer than 337ter revealed that four of the eight amino acids identified initially provided the minimum length required for the protein to acquire cell surface expression. This was shown by the production of mature receptor (V2R-341ter) detectable in SDS-PAGE, which mediated arginine vasopressin stimulation of adenylyl cyclase activity and bound ligand. In addition, the identity of amino acid 340 was found to play a role in this phenomenon. In conclusion, these data demonstrate that the V2R R337ter is nonfunctional because it does not reach the plasma membrane and that the minimal protein length required for translocation of the V2R to the cell surface is sufficient to confer function to the receptor protein. They also suggest the existence of a protein quality control in the endoplasmic reticulum independent of glycosylation.
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PMID:An X-linked NDI mutation reveals a requirement for cell surface V2R expression. 917 Dec 34

A quantitative study regarding the age-related changes occurring in the nucleus and the somatic organelles of neurosecretory magnocellular neurons of the hypothalamo neurohypophyseal system (HNS) was carried out in the hamster at six age-points during animal life. The magnocellular cells of both parts of the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of male Syrian hamsters between 3 and 30 months of age were examined ultrastructurally. Cells of all age groups present the same morphological ultrastructure. Standard manual morphometric techniques are used to calculate the following parameters related directly or indirectly with cellular activity: nuclear area, nucleolar area, nuclear invagination index and volumetric fractions of some intracellular structures (Golgi apparatus, mitochondria, rough endoplasmic reticulum and lipofuscin). With respect to the cell nucleus, the parameters are not modified during aging. No significant differences in the volume density of subcellular components, except lipofuscin, were detected at the age groups studies. However, there is a positive linear trend among all parameters and age except for the rough endoplasmic reticulum. Our results suggest maintenance of the synthetic activity of the magnocellular neurons in the hamster during aging but in no case an increase in their metabolic activity.
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PMID:The magnocellular neurosecretory system of the hamster hypothalamus: an ultrastructural and morphometric study during lifetime. 922 33

We examined the expression of regulated endocrine-specific protein of 18-kD (RESP18) in selected peptidergic and catecholaminergic neurons of adult rat brain. In the hypothalamic paraventricular, supraoptic, and accessory nuclei, RESP18 mRNA was highly expressed in neurons immunostained for oxytocin and vasopressin. RESP18 mRNA was also highly expressed in paraventricular nucleus neurons immunostained for corticotropin-releasing hormone, thyrotropin-releasing hormone, and somatostatin. RESP18 mRNA was expressed in POMC cells of the arcuate nucleus, in neuropeptide Y cells of the dorsal tegmental nucleus, lateral reticular nucleus, and hippocampus, and in brainstem catecholaminergic neurons. RESP18 mRNA expression was high in all paraventricular and arcuate neurons, but RESP18 protein was detectable in the perikarya of a subset of these neurons, suggesting an important post-transcriptional component to the regulation of RESP18 expression. RESP18 antisera immunostained perikarya but not axon fibers or terminals. Sub-cellular fractionation of homogenates of several hypothalamic nuclei identified RESP18 protein in fractions enriched in endoplasmic reticulum. The presence of 22- and 24-kD RESP18 isoforms in the neural lobe of the pituitary indicated that some RESP18 protein exited the endoplasmic reticulum. The post-transcriptional regulation of RESP18 expression and localization of RESP18 protein primarily to the endoplasmic reticulum suggests that RESP18 plays a regulatory role in peptidergic neurons.
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PMID:Expression of RESP18 in peptidergic and catecholaminergic neurons. 928 14

Ca2+ functions as an intracellular signal to transfer hormonal messages to different cellular compartments, including mitochondria, where it activates intramitochondrial Ca2(+)-dependent enzymes. However, excessive mitochondrial Ca2+ uptake can promote the mitochondrial permeability transition (MPT), a process known to be associated with cell injury. The factors controlling mitochondrial Ca2+ uptake and release in intact cells are poorly understood. In this paper, we investigate mitochondrial Ca2+ accumulation in intact hepatocytes in response to the elevation of cytosolic Ca2+ levels ([Ca2+]c) induced either by a hormonal stimulus (vasopressin), or by thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump. After stimulation, cells were rapidly permeabilized for the determination of the mitochondrial Ca2+ content (Ca2+(m)) and to analyze the susceptibility of the mitochondria to undergo the MPT. Despite very similar levels of [Ca2+]c elevation, vasopressin and thapsigargin had markedly different effects on mitochondrial Ca2+ accumulation. Vasopressin caused a rapid (< 90 sec), but modest (< 2 fold) increase in Ca2+(m) that was not further increased during prolonged incubations, despite a sustained [Ca2+]c elevation. By contrast, thapsigargin induced a net Ca2+ accumulation in mitochondria that continued for up to 30 min and reached Ca2+(m) levels 10-20 fold over basal. Accumulation of mitochondrial Ca2+ was accompanied by a markedly increased susceptibility to undergo the MPT. Both mitochondrial Ca2+ accumulation and MPT activation were modulated by treatment of the cells with inhibitors of protein kinases and phosphatases. The results indicate that net mitochondrial Ca2+ uptake in response to hormonal stimulation is regulated by processes that depend on protein kinase activation. These controls are inoperative when the cytosol is flooded by Ca2+ through artificial means, enabling mitochondria to function as a Ca2+ sink under these conditions.
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PMID:Hormonal stimulation, mitochondrial Ca2+ accumulation, and the control of the mitochondrial permeability transition in intact hepatocytes. 930 83

Pituitary adenylate cyclase-activating polypeptide (PACAP) was localized in nerve terminals that innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON). PACAP receptor (PACAPR) mRNA was expressed at high-levels in AVP-containing neurons in the SON, but at very low-levels in oxytocin-containing neurons. PACAPR-like immunoreactivity was found in SON and it was observed in the post-synaptic membranes as well as on the rough endoplasmic reticulum and cytoplasmic matrices in the magnocellular neurons. Doses of PACAP in the nanomolar range increased cytoplasmic Ca2+ concentrations ([Ca2+]i) in AVP-containing neurons; the increase in [Ca2+]i was inhibited by a protein kinase A blocker. These findings suggest that PACAP serves as a transmitter and/or modulator and the activation of PACAPR stimulates a cAMP-protein kinase A pathway which in turn evokes the Ca2+ signaling system. It is hypothesized that PACAP regulates the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP): a novel regulator of vasopressin-containing neurons. 931 Mar 97

The roles of a monomeric GTP-binding regulatory protein in the activation of store-activated plasma membrane Ca2+ channels and in the release of Ca2+ from the smooth endoplasmic reticulum (SER) in rat liver parenchymal cells were investigated with the use of freshly isolated rat hepatocytes and rat liver microsomes. A low concentration (approx. 130 microM intracellular) of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) activated Ca2+ inflow in intact hepatocytes in the absence of an agonist, whereas a high concentration (approx. 530 microM intracellular) of GTP-S- or guanosine 5'-[betagamma-imido]triphosphate (p[NH]ppG) inhibited the Ca2+ inflow induced by inhibitors of the activity of the endoplasmic-reticulum Ca2+-ATPase (SERCA) and by vasopressin. GTP (530 microM) prevented the inhibition of Ca2+ inflow by GTP-S- and p[NH]ppG. Brefeldin A and the peptide human Arf-1-(2-17), which inhibit many functions of ADP ribosylation factor (Arf) proteins, inhibited the Ca2+ inflow induced by SERCA inhibitors and vasopressin, and altered the profile of Ca2+ release from the SER. These effects were observed at concentrations of Brefeldin A and Arf-1-(2-17) comparable with those that inhibit the functions of Arf proteins in other systems. Succinylated Arf-1-(2-17) had a negligible effect on Ca2+ inflow. GTP[S] and Arf-1-(2-17) completely inhibited the synergistic action of GTP and Ins(1,4,5)P3 in releasing 45Ca2+ from rat liver microsomes loaded with 45Ca2+. AlF4(-) (under conditions expected to activate trimeric G-proteins) and succinylated Arf-1-(2-17) had no effect on GTP/Ins(1,4,5))3-induced 45Ca2+ release, and a mastoparan analogue caused partial inhibition. Arf-1-(2-17) did not inhibit 45Ca2+ release induced by either thapsigargin or ionomycin. It is concluded that a low-molecular-mass G-protein, most probably a member of the Arf protein family, is required for store-activated Ca2+ inflow in rat hepatocytes. The idea that the role of this G-protein is to maintain a region of the SER in the correct intracellular location is discussed briefly.
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PMID:Evidence that a low-molecular-mass GTP-binding protein is required for store-activated Ca2+ inflow in hepatocytes. 937 2

The subcellular localization and functional significance of neuronal nicotinic acetylcholine receptor alpha4-subunits were investigated in the rat hypothalamic supraoptic nucleus. A high level of alpha4 mRNA expression was found in the magnocellular neurons in the supraoptic nucleus. Strong immunoreactitivy for alpha4 in neurons of the supraoptic nucleus was detected in the rough endoplasmic reticulum and cytoplasmic matrix, although it was very weak in the Golgi apparatus, except for the transport vesicles. Immunoreactivity for alpha4 was detected in both the pre-synaptic axon terminals and post-synaptic axon terminals. A high level of signals for vasopressin mRNA was detected in the supraoptic nucleus after the animals were injected s.c. with nicotine. These findings suggest that alpha4-containing subtypes are synthesized in the rough endoplasmic reticulum and transported to the plasma membrane and serve as pre- and post-synaptic nicotinic acetylcholine receptors. Nicotine may up-regulate vasopressin gene expression in the supraoptic nucleus, acting through nicotinic acetylcholine receptors.
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PMID:Neuronal nicotinic acetylcholine receptor in the hypothalamus: morphological diversity and neuroendocrine regulations. 938 62


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