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)

Endogenous opioid peptides are present in cerebral perivascular nerves and in the CSF, and their concentrations are changing in response to stimuli that activate regulatory mechanisms of the cerebral circulation (e.g., alterations of the perfusion pressure or changes of the arterial O2 tension). Opiate receptors are expressed in the cells of the CNS and the cerebrovascular bed, and their activation modulates the function of other vasoregulatory mechanisms (i.e., the autonomic nervous system, nitric oxide, prostanoids, vasopressin) that are involved in the control of the cerebrovascular tone. The direct vasomotor effects of opioid peptides and opiates on the cerebral arteries under in vitro or in situ conditions appear to be weak or absent in several species. However, Met- and Leu-enkephalin induce pial arterial vasodilation in the newborn pig. In this species, beta-endorphin acts as a constrictor, whereas dynorphin may induce either dilation or constriction depending on the experimental conditions. The influence of exogenously applied natural and synthetic opioids on the cerebral blood flow (CBF) is determined mainly by their metabolic, neuronal, and respiratory effects. Hypothalamic and pituitary circulations are especially sensitive to opioids. Under resting conditions, endogenous opioid peptides do not participate in the regulation of the cerebrovascular tone and CBF. On the other hand, mu and delta opiate receptor stimulation by endogenous opioid peptides, interacting with other vasoactive factors, obviously contributes to the hypoxia- and hypercapnia-induced cerebral vasodilation. Furthermore, endogenous opioid mechanisms are involved in the autoregulation of the hypothalamic blood flow. Thus, the endogenous opioid system may well represent a latent regulatory mechanism, which is of limited importance under basal conditions, but becomes more important under conditions of stress. Synthetic exogenous opioids do not appear to influence the hypoxic or hypercapnic CBF responses or the cerebral autoregulatory process.
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PMID:Opiate receptor-mediated mechanisms in the regulation of cerebral blood flow. 896 68

The amiloride-sensitive epithelial Na+ channel is formed by the assembly of three homologous subunits alpha, beta and gamma. The channel is characterized by its sensitivity to amiloride and to some amiloride derivatives, such as phenamil and benzamil, by its small unitary conductance (approximately 5pS), by its high selectivity for lithium and sodium, and by its slow kinetics. The alpha, beta, and gamma proteins share significant identity with degenerins, a family of proteins found in the mechanosensory neurons and interneurons of the nematode Caenorhabditis elegans. They are also homologous to FaNaCh, a protein from Helix aspersa nervous tissues, which corresponds to a neuronal ionotropic receptor for the Phe-Met-Arg-Phe-amide peptide. All these proteins contain a large extracellular loop, located between two transmembrane alpha-helices. The NH2 and COOH terminal segments are cytoplasmic, and contain potential regulatory segments that are able to modulate the activity of the channel. In Liddle syndrome, in which patients develop a form of genetic hypertension, mutations within the cytoplasmic COOH terminal of the beta and gamma chains of the epithelial Na+ channel lead to a hyper-activity of the channel. Epithelial Na+ channel activity is tightly controlled by several distinct hormonal systems, including corticosteroids and vasopressin. In kidney and colon, aldosterone is the major sodium-retaining hormone, acting, by stimulation of Na+ reabsorption through the epithelium. In the distal colon from steroid-treated animals, a large increase of the beta and gamma subunits transcription is observed, whereas the alpha subunit remains constitutively transcribed. In kidney, RNA levels of the three subunits are not significantly altered by aldosterone, suggesting that other mechanisms control Na+ channel activity in that tissue. In lung, the glucocorticoids are the positive regulators of the channel activity, especially around birth, and act via an increased transcription of the three subunits.
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PMID:[The amiloride sensitive sodium channel]. 901 66

Low intravenous doses of endotoxin [lipopolysaccharide (LPS), 0.7 microgram/kg] induce monophasic fever, increase anterior and posterior pituitary hormone release, and enhance hypothalamic c-Fos expression in pigs, all of which can be prevented by indomethacin (Ind). The present study shows that the synthetic corticosteroid dexamethasone (Dex, 5 mg/kg) has a similar action to Ind and, when given alone, lowers core temperature. In addition, the corticosteroid synthesis inhibitor metyrapone (Met, 3.3 mg/kg, every one-half hour) reduces LPS fever and amplifies the effect of LPS on vasopressin, but not on oxytocin, release. The similar actions of Dex and Ind suggest that phospholipase A2 pathways controlling prostaglandin synthesis mediate the responses of prepubertal pigs to immunological challenge with LPS. The increased vasopressin release induced when animals receiving Met are also given LPS supports findings in other nonrodent species indicating an inverse relationship between cortisol and vasopressin. The attenuation of LPS fever by Met is suggestive of an endogenous antipyretic mechanism associated with enhanced neurohypophysial vasopressin secretion.
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PMID:Interrelated adrenocortical and neurohypophysial responses associated with fever in endotoxin-treated pigs. 932 84

A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 microM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With M(r) 85 kDa the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 microM) and for atrial natriuretic peptide (Km = 5 microM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.
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PMID:A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide. 1034 68

The neural connections and neurotransmitter content of the suprachiasmatic nucleus and intergeniculate leaflet have been characterized thoroughly in only a few mammalian species, primarily nocturnal rodents. Few data are available about the neural circadian timing system in diurnal mammals, particularly those for which the formal characteristics of circadian rhythms have been investigated. This paper describes the circadian timing system in the diurnal rodent Octodon degus, a species that manifests robust circadian responses to photic and non-photic (social) zeitgebers. Specifically, this report details: (i) the distribution of six neurotransmitters commonly found in the suprachiasmatic nucleus and intergeniculate leaflet; (ii) the retinohypothalamic tract; (iii) the geniculohypothalamic tract; and (iv) retinogeniculate projections in O. degus. Using immunocytochemistry, neuropeptide Y-immunoreactive, serotonin-immunoreactive and [Met]enkephalin-immunoreactive fibers and terminals were detected in and around the suprachiasmatic nucleus; vasopressin-immunoreactive cell bodies were found in the dorsomedial and ventral suprachiasmatic nucleus; vasoactive intestinal polypeptide-immunoreactive cell bodies were located in the ventral suprachiasmatic nucleus; [Met]enkephalin-immunoreactive cells were located sparsely throughout the suprachiasmatic nucleus; and substance P-immunoreactive fibers and terminals were detected in the rostral suprachiasmatic nucleus and surrounding the nucleus throughout its rostrocaudal dimension. Neuropeptide Y-immunoreactive and [Met]enkephalin-immunoreactive cells were identified in the intergeniculate leaflet and ventral lateral geniculate nucleus, as were neuropeptide Y-immunoreactive, [Met]enkephalin-immunoreactive, serotonin-immunoreactive and substance P-immunoreactive fibers and terminals. The retinohypothalamic tract innervated both suprachiasmatic nuclei equally; in contrast, retinal innervation to the lateral geniculate nucleus, including the intergeniculate leaflet, was almost exclusively contralateral. Bilateral electrolytic lesions that destroyed the intergeniculate leaflet depleted the suprachiasmatic nucleus of virtually all neuropeptide Y- and [Met]enkephalin-stained fibers and terminals, whereas unilateral lesions reduced fiber and terminal staining by approximately half. Thus, [Met]enkephalin-immunoreactive and neuropeptide Y-immunoreactive cells project equally and bilaterally from the intergeniculate leaflet to the suprachiasmatic nucleus via the geniculohypothalamic tract in degus. This is the first report examining the neural circadian system in a diurnal rodent for which formal circadian properties have been described. The data indicate that the neural organization of the circadian timing system in degus resembles that of the most commonly studied nocturnal rodents, golden hamsters and rats. Armed with such data, one can ascertain differences in the functional organization of the circadian system between diurnal and nocturnal mammals.
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PMID:Suprachiasmatic nucleus and intergeniculate leaflet in the diurnal rodent Octodon degus: retinal projections and immunocytochemical characterization. 1042 2

The NT2 cell line, which was derived from a human teratocarcinoma, exhibits properties that are characteristic of a committed neuronal precursor at an early stage of development. NT2 cells can be induced by retinoic acid to differentiate in vitro into postmitotic central nervous system (CNS) neurons (NT2-N cells). The commitment of NT2-N cells to a stable neuronal phenotype is irreversible. Because it may be possible to transplant these human neurons to compensate for neuronal loss after traumatic injuries or neurodegenerative diseases of the CNS, knowledge of their phenotype is essential. This study aimed to characterize in detail the neurotransmission phenotype of NT2-N cells by using immunocytochemical methods. Single peroxidase immunostaining demonstrated that NT2-N cells expressed the gamma-aminobutyric acidergic (GABAergic), catecholaminergic, and cholinergic phenotypes to a large extent and expressed the serotonergic phenotype to a minor extent. NT2-N cells also expressed different neuropeptides, such as neuropeptide Y, oxytocin, vasopressin, calcitonin gene-related peptide, and Met- and Leu-enkephalin. Double fluorescence immunostaining further indicated that a large number of NT2-N cells could express GABA and another neurotransmitter or neuropeptide at the same time. Finally, electron microscopy demonstrated that these NT2 neurons elaborate classical synaptic contacts. The multipotentiality of these neurons, combined with their apparent functionality, suggests that they may represent useful material for a variety of therapeutic approaches aimed at replacing dead neurons after neurodegenerative diseases or lesions of the CNS.
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PMID:Human NT2 neurons express a large variety of neurotransmission phenotypes in vitro. 1086 14

The consequences of purinoceptor activation on calcium signalling, inositol phosphate metabolism, protein secretion and the actin cytoskeleton were demonstrated in the WRK-1 cell line. Extracellular ATP was used as a secretagogue to induce a rise in intracellular Ca(2+) concentration ([Ca(2+)](i)), acting via P2x purinergic receptors, which causes actin skeleton disaggregation and protein secretion. ATP bound specifically to purinergic receptors, with Ki of 0.8 microM. The magnitude order for binding of different nucleotides was alpha beta-Met-ATP >or= dATPalphaS > ATP >or= ADP > UTP > AMP > suramin. No increase in inositol phosphates (IPs) was observed after ATP application suggesting that the purinergic sites in WRK-1 cells are not of a P2y type. ATP (1-100 microM) caused a concentration-dependent increase in [Ca(2+)](i)(EC(50)= 30 microM). The responses were reproducible without any desensitization over several applications. The response to ATP was abolished when extracellular calcium ([Ca(2+)](e)) was reduced to 100 nM. A non-specific purinergic antagonist, suramin, reversibly inhibited the ATP-response suggesting that ATP is able to bind to P2x purinergic sites to trigger Ca(2+) entry and increase of [Ca(2+)](i). ATP induced a concentration-dependent disaggregation of actin and exocytotic release of proteins both, which were dependent upon [Ca(2+)](e). Similarly, alpha,beta-Met-ATP, a potent P2x agonist also stimulated Ca(2+) mobilization, actin network destructuration, and protein release. In the isolated rat neurohypophysial nerve terminals, ATP was shown to act as a physiological stimulus for vasopressin release via Ca(2+) entry through a P2x receptor [6]. Here, we show that in these nerve terminals, ATP is also able to induce actin disaggregation by a Ca(2+) dependent mechanism. Thus, actin cytoskeleton alterations induced by ATP through activation of P2x receptors could be a prelude to exocytosis.
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PMID:ATP induces intracellular calcium increases and actin cytoskeleton disaggregation via P2x receptors. 1129 87

Apelin, a peptide recently isolated from bovine stomach tissue extracts, has been identified as the endogenous ligand of the human orphan APJ receptor. We established a stable Chinese hamster ovary (CHO) cell line expressing a gene encoding the rat apelin receptor fused to the enhanced green fluorescent protein, to investigate internalization and the pharmacological profile of the apelin receptor. Stimulation of this receptor by the apelin fragments K17F (Lys1-Phe-Arg-Arg-Gln-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe17) and pE13F (pGlu5-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe17) resulted in a dose-dependent inhibition of forskolin-induced cAMP production and promoted its internalization. In contrast, the apelin fragments R10F (Arg8-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe17) and G5F (Gly13-Pro-Met-Pro-Phe17) were inactive. The physiological role of apelin and its receptor was then investigated by showing for the first time in rodent brain: (i) detection of apelin neurons in the supraoptic and paraventricular nuclei by immunohistochemistry with a specific polyclonal anti-apelin K17F antibody; (ii) detection of apelin receptor mRNA in supraoptic vasopressinergic neurons by in situ hybridization and immunohistochemistry; and (iii) a decrease in vasopressin release following intracerebroventricular injection of K17F, or pE13F, but not R10F. Thus, apelin locally synthesized in the supraoptic nucleus could exert a direct inhibitory action on vasopressinergic neuron activity via the apelin receptors synthesized in these cells. Furthermore, central injection of pE13F significantly decreased water intake in dehydrated normotensive rats but did not affect blood pressure. Together, these results suggest that neuronal apelin plays an important role in the central control of body fluid homeostasis.
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PMID:Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. 1135 74

To facilitate structure-function relationship studies of the V2 vasopressin receptor, a prototypical G(s)-coupled receptor, we generated V2 receptor-expressing yeast strains (Saccharomyces cerevisiae) that required arginine vasopressin-dependent receptor/G protein coupling for cell growth. V2 receptors heterologously expressed in yeast were unable to productively interact with the endogenous yeast G protein alpha subunit, Gpa1p, or a mutant Gpa1p subunit containing the C-terminal G alpha(q) sequence (Gq5). In contrast, the V2 receptor efficiently coupled to a Gpa1p/G alpha(s) hybrid subunit containing the C-terminal G alpha(s) sequence (Gs5), indicating that the V2 receptor retained proper G protein coupling selectivity in yeast. To gain insight into the molecular basis underlying the selectivity of V2 receptor/G protein interactions, we used receptor saturation random mutagenesis to generate a yeast library expressing mutant V2 receptors containing mutations within the second intracellular loop. A subsequent yeast genetic screen of about 30,000 mutant receptors yielded four mutant receptors that, in contrast to the wild-type receptor, showed substantial coupling to Gq5. Functional analysis of these mutant receptors, followed by more detailed site-directed mutagenesis studies, indicated that single amino acid substitutions at position Met(145) in the central portion of the second intracellular loop of the V2 receptor had pronounced effects on receptor/G protein coupling selectivity. We also observed that deletion of single amino acids N-terminal of Met(145) led to misfolded receptor proteins, whereas single amino acid deletions C-terminal of Met(145) had no effect on V2 receptor function. These findings highlight the usefulness of combining receptor random mutagenesis and yeast expression technology to study mechanisms governing receptor/G protein coupling selectivity and receptor folding.
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PMID:Single amino acid substitutions and deletions that alter the G protein coupling properties of the V2 vasopressin receptor identified in yeast by receptor random mutagenesis. 1137 90

There is growing evidence of local protein synthesis in neuronal dendrites, especially in relation to synaptic activity. The hypothalamic magnocellular system is a robust model for peptidergic neurons, especially for the study of dendrites. Quantitative electron microscopy, immunocytochemistry and non-radioactive in situ hybridization (with tyramide signal amplification) were used to compare dendrites of magnocellular neurons in the supraoptic nucleus of wild-type rats and of homozygous Brattleboro (BB) rats which are subject to long-term hyper-osmotic stimulation because they cannot secrete vasopressin. The dendrites contained free polyribosomes, cisterns of rough endoplasmic reticulum (ER) and small Golgi-like elements. These were clustered in the dendrites, mostly near the plasma membrane. All were increased in amount in the enlarged dendrites of the BB rats. The presence of polyribosomes and cisterns of rER implies that both cytosolic and membrane-inserting proteins are synthesized in the dendrites. The ER marker protein disulfide isomerase extended far into dendrites, but Golgi element markers (mid-Golgi and trans-Golgi network) were distributed mainly in their proximal parts. In BB rats, all the labeling was stronger. 28S rRNA, initiator tRNA(Met), and poly(A) mRNA were revealed extending into proximal and middle parts of dendrites where intensely reactive punctate structures were common. 28S rRNA could be detected in the distal parts of the dendrites. The length of positively stained dendrites was increased significantly for all these RNAs in BB rats. The results provide morphological evidence that magnocellular dendrites have the capacity for local protein syntheses and that this is increased in chronic hyperosmotic stress.
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PMID:Protein synthetic machinery in the dendrites of the magnocellular neurosecretory neurons of wild-type Long-Evans and homozygous Brattleboro rats. 1186 Nov 24


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