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)

Endothelins (ET-1, ET-2 and ET-3) are a family of 21 amino acid peptides produced by endothelial cells. They are thought to regulate the local vasomotor tone with endothelium-derived relaxing factors. ETs are the most potent vasoconstrictor substances yet identified and veins and renal vasculature are the most sensitive targets. They reduce cardiac output and have positive inotropic and chronotropic effects. ETs increase the secretion of atrial natriuretic peptide (ANP), aldosterone and catecholamines but reduce renal blood flow and glomerular filtration and they also have mitogenic properties. ETs bind to receptors (ETA and ETB), activate phospholipase C, modulate intracellular Ca2+ concentration and open Ca2+ channels. Vasoactive agents (adrenaline, angiotensin, vasopressin, thrombin, endotoxins) and hypoxia stimulate the release of ET and also ET gene expression. Raised concentrations of plasma ET have been found to occur in several clinical conditions such as hypertension, myocardial infarction, cardiogenic shock, pregnancy induced hypertension, arteriosclerosis, Raynaud's disease, subarachnoid haemorrhage, uraemia, ulcerative colitis, Crohn's disease and surgical operations suggesting that ETs have a role in several patophysiological processes.
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PMID:Endothelin peptides: biological activities, cellular signalling and clinical significance. 138 14

Endothelin (ET) is thought to be involved in the central regulation of body water metabolism. A recent perfusion study of rat hypothalamus showed that ET has a direct stimulatory action on arginine-vasopressin (AVP) release. This study was undertaken to investigate whether ET acts directly on AVP release for supraoptic nucleus (SON) neurons, using brain slices containing only the SON. It was demonstrated that ET inhibited the AVP release dose-dependently from 10(-11) M to 10(-6) M. No difference of the effects of ET-1 and ET-3 on AVP release was observed. These results suggest that ET directly inhibits SON neurons through the ETB receptor.
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PMID:Inhibitory effects of endothelin-3 on vasopressin release from rat supraoptic nucleus in vitro. 143 27

In this study, the short-term regulation of endothelin-1-(ET-1) induced phosphoinositide (PI) hydrolysis and arachidonic acid release were investigated in cultured rat aortic smooth-muscle cells. ET-1, but not the ETB-selective peptide sarafotoxin (SFX) S6c, induced a dose-dependent increase in [3H]inositol phosphate release (EC50 = 0.4 +/- 0.1 nM). ET-3 stimulated this response only at concentrations > 0.1 microM. The ETA receptor antagonist BQ-123 inhibited ET-1-induced PI turnover, with an IC50 value of 97 +/- 15 nM. Pre-exposure of intact cells to ET-1 resulted in a 72% and 73% reduction in the ability of ET-1 or SFX S6b, respectively, to stimulate [3H]inositol phosphate release, without affecting the response to vasopressin. In contrast, PI turnover induced by ET-1 or SFX S6b was only slightly lowered, by 28% and 22%, after a 30-min preincubation period with SFX S6b. ET-1, but not SFX S6c, also stimulated [3H]arachidonic acid release by two-fold (EC50 = 3 +/- 0.8 nM). Pretreatment of intact cells with neomycin or phorbol-12-myristate-13-acetate resulted in a 49% and 44% inhibition of ET-1-induced [3H]inositol phosphate accumulation but did not decrease ET-1-stimulated [3H]arachidonic acid release, suggesting that these responses are separately regulated events in these cells.
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PMID:Short-term regulation of endothelin receptor-mediated phosphoinositide hydrolysis and arachidonic acid release in A7r5 smooth-muscle cells. 750 34

We characterized the endothelin (ET) receptor subtypes responsible for signal transduction in cultured porcine kidney epithelial LLC-PK1 cells. Both ET-1 (IC50, 43 pM) and ET-3 (IC50, 46 pM) inhibited the binding of [125I]ET-1 to LLC-PK1 cells to a similar extent. The binding affinity of LLC-PK1 cells was about 10,000 times higher for the ETB antagonist BQ-788 [N-cis-2,6-dimethyl-piperidinocarbonyl-L-tau-metylleucyl-D-+ ++Nin- methoxycarbonyltryptophanyl-D-norleucine] (IC50, 1.3 nM) than for the ETA antagonist BQ-123 [cyclo-(D-Trp-D-Asp-Pro-D-Val-Leu)] (IC50, 14 microM). ET-1 enhanced cyclic GMP (cGMP) production, but reduced vasopressin- and forskolin-stimulated cyclic AMP (cAMP) production. Both effects of ET-1 were antagonized by BQ-788, but not by BQ-123. The cAMP decrease, but not the cGMP increase, in response to ET-1 was inhibited by pertussis toxin, suggesting that the former response is mediated by pertussis toxin-sensitive Gi, whereas the latter is mediated by a pertussis toxin-insensitive G-protein. Therefore, the ETB receptors in LLC-PK1 cells couple to the two types of signal transduction cascades to reduce cAMP production and stimulate cGMP production via distinct G-proteins. ET-1 and probably also ET-3 may play a role in the regulation of renal epithelial transport by decreasing cAMP and increasing cGMP.
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PMID:Endothelin ETB receptors couple to two distinct signaling pathways in porcine kidney epithelial LLC-PK1 cells. 793 50

The effectiveness of intradermal (i.d.) BQ-123 (cyclo[D-Asp-Pro-D-Val-Leu-D-Trp]) and i.d. Ro 47-0203 (bosentan, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyr imidin-4 - yl]-benzene-sulfonamide) has been evaluated on local microvascular responses to endothelin-1 and endothelin-3, measured by a multiple site 133Xe clearance technique in rat skin in vivo. Intradermal injection of endothelin-1 (0.3 pmol/site) and endothelin-3 (10 pmol/site) induced a similar (approximately 50-60%) decrease in basal blood flow in rat skin. BQ-123 (3-1000 pmol/site), a selective endothelin ETA receptor antagonist, caused a significant dose-dependent decrease in the vasoconstriction induced by endothelin-1 (P < 0.05) but was less effective on vasoconstriction induced by endothelin-3. Bosentan (3-1000 pmol/site), a new non-peptide mixed antagonist of endothelin ETA and endothelin ETB receptors, significantly reduced the vasoconstriction induced by endothelin-1 but was less effective than BQ-123. BQ-123 and bosentan were similarly effective as antagonists of endothelin-3. BQ-123 and bosentan had no effect on basal blood flow and no inhibitory activity on vasoconstriction induced by vasopressin (0.03 pmol/site) or phenylephrine (300 pmol/site). These findings indicate that BQ-123 and bosentan are effective and selective inhibitors of the vasoconstriction induced by endothelins in the rat skin microvasculature.
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PMID:Effect of BQ-123 and Ro 47-0203 (bosentan) on endothelin-induced vasoconstriction in the rat skin. 795 19

Addition of endothelin-1 or endothelin-3 to rat renal papillary tubules produced a dose-dependent inhibition of the cAMP response to vasopressin stimulation. The average EC50 values were 1.1 +/- 0.6 and 2.6 +/- 1.1 nM, respectively, indicating mediation by an endothelin ETB receptor. Phorbol myristate acetate (1 microM) also inhibited the vasopressin-cAMP response and this inhibition was not additive with that to endothelin, indicating that the endothelin inhibition is mediated by activation of protein kinase C. These findings demonstrate functionally relevant endothelin ETB receptors on renal papillary tubules. Such receptors are a possible target for endothelin-3 produced within the kidney.
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PMID:Functional endothelin ETB receptors on renal papillary tubules. 825 66

We characterized the endothelin (ET) receptor subtype responsible for the inhibition of vasopressin (AVP)-induced increases in osmotic water permeability (Pf) and cAMP accumulation in rat inner medullary collecting ducts (IMCD). ET-1 (10 nM) produced a rapid and transient decrease in AVP-stimulated Pf from 1241 +/- 112 to 224 +/- 38 microns/sec. At the same concentration (10 nM), the selective ETB receptor agonist sarafotoxin 6c (S6c) produced the same degree of inhibition with a time course identical to that of ET-1. Exposure of IMCDs to the ETA-selective antagonist BQ123 (100 nM) had no effect on ET-1-induced inhibition of AVP-dependent Pf. In suspensions of IMCD cells, ET-1, ET-3 or S6c produced concentration-dependent inhibition of AVP-stimulated cAMP accumulation to the same extent and with similar potencies (IC50 = 10-30 nM). BQ123 (1 nM to 10 microM) had no effect on ET-1-induced inhibition of AVP-stimulated cAMP formation. Saturation binding experiments with radiolabeled ET-1 and the selective ETB agonist IRL1620 and competition binding studies with selective ETA and ETB receptor ligands demonstrated that > or = 80% of the ET-1 binding sites in IMCD membranes were of the ETB subtype. Therefore, results from functional, biochemical and binding studies suggest that the ETB receptor is the ET receptor subtype that inhibits AVP action in the rat IMCD.
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PMID:Endothelin inhibits vasopressin action in rat inner medullary collecting duct via the ETB receptor. 826 61

We have demonstrated in liver from male rats that both endothelin A (ETA) and ETB receptors coexist in equal proportion and that ETA receptors mediate a calcium-dependent activation of glycogenolysis. We describe here a sex difference in endothelin action in hepatocytes because, in female rats, 80% of the ET receptors are of ETB type and, accordingly, activation of glycogenolysis is an ETB-mediated process (EC50 = 0.03 pM). ET-1 stimulation of glycogenolysis in female rats was consecutive to activation of phosphatidylinositol 4,5-bisphosphate hydrolysis (EC50 = 0.03 pM) and to inhibition of the calcium extrusion pump (IC50 = 0.03 pM) in plasma membranes, with ET-1 approximately sarafotoxin S6C approximately ET-3. Endothelin regulation of each effector was potentiated by GTP gamma S. ET-1 did not stimulate adenylyl cyclase activity. To identify the nature of the guanine nucleotide regulatory proteins (G protein(s)) coupling ETB receptors to each effector, we used antibodies against the COOH terminus of different G protein alpha subunits. Antibodies reactive with Gs alpha (RM) blocked ET-1 inhibition of the calcium pump, while they did not affect ET-1 stimulation of phospholipase C. Antibodies reactive with Gq alpha (QL) dose-dependently antagonized stimulation of phospholipase C by ET-1 and vasopressin, without affecting ET-1 inhibition of the calcium pump. Antibodies reactive with Gi1 alpha/Gi2 alpha (AS) had no effect on either system. We conclude that the calcium signal provoked by endothelins in hepatocyte is not only consecutive to activation of phospholipase C but also to inhibition of the plasma membrane calcium pump, each effector being coupled to ETB receptors by different G proteins, Gq, and Gs.
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PMID:Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs and Gq in rat liver. 829 32

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

The ubiquitously expressed heterotrimeric guanine nucleotide-binding proteins (G-proteins) G12 and G13 have been shown to activate the small GTPase Rho. Rho stimulation leads to a rapid remodeling of the actin cytoskeleton and subsequent stress fiber formation. We investigated the involvement of G12 or G13 in stress fiber formation induced through a variety of Gq/G11-coupled receptors. Using fibroblast cell lines derived from wild-type and Galphaq/Galpha11-deficient mice, we show that agonist-dependent activation of the endogenous receptors for thrombin or lysophosphatidic acid and of the heterologously expressed bradykinin B2, vasopressin V1A, endothelin ETA, and serotonin 5-HT2C receptors induced stress fiber formation in either the presence or absence of Galphaq/Galpha11. Stress fiber assembly induced through the muscarinic M1 and the metabotropic glutamate subtype 1alpha receptors was dependent on Gq/G11 proteins. The activation of the Gq/G11-coupled endothelin ETB and angiotensin AT1A receptors failed to induce stress fiber formation. Lysophosphatidic acid, B2, and 5-HT2C receptor-mediated stress fiber formation was dependent on Galpha13 and involved epidermal growth factor (EGF) receptors, whereas thrombin, ETA, and V1A receptors induced stress fiber accumulation via Galpha12 in an EGF receptor-independent manner. Our data demonstrate that many Gq/G11-coupled receptors induce stress fiber assembly in the absence of Galphaq and Galpha11 and that this involves either a Galpha12 or a Galpha13/EGF receptor-mediated pathway.
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PMID:Differential involvement of Galpha12 and Galpha13 in receptor-mediated stress fiber formation. 1036 36


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