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)

Losartan, a nonpeptide angiotensin II receptor antagonist, was used to establish the role of brain AT1 angiotensin II receptor subtype on the natriuretic, antidiuretic, and dipsogenic actions of centrally administered renin. Intracerebroventricular administration of renin reduces urine volume and increases sodium excretion and water intake in conscious, male, hydrated rats. Losartan (3 or 10 mg/kg, sc) reduced the increased sodium excretion and totally inhibited the antidiuretic action induced by intracerebroventricular renin. When both renin and Losartan were given intracerebroventricularly, at the highest dose, there was a potent inhibition of the antidiuretic and natriuretic actions. Peripheral and central administration of the AT1 receptor blocker significantly lengthened the onset of drinking behavior and reduced the cumulative water intake observed after intracerebroventricular injection of renin. Our results strongly suggest that the brain AT1 receptor subtype mediates the physiologic actions of angiotensin II, such as drinking behavior, the increase in sodium excretion, and vasopressin release.
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PMID:Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin. 845 3

Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominantly express AT1 ANG II receptors. In contrast, AT2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT1 and AT2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 microliters) were determined 10 minutes after i.c.v. injection of either the AT1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 10.0 micrograms), the AT2 receptor ligand PD 123319 (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both. In control rats, i.c.v. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II-induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG-II-induced pressor effects may involve activation of multiple receptor subtypes.
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PMID:Functional roles of brain AT1 and AT2 receptors in the central angiotensin II pressor response in conscious young spontaneously hypertensive rats. 849 Oct 41

The present study investigates the effect of angiotensin II and LR-B/081 (-methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetra-zol-5-yl) [1,1'-biphenyl]-4-yl] methyl]-1(6H)-pyrimidinyl] methyl]-3-thiophenecarboxylate), a novel non-peptide angiotensin II receptor antagonist, on both early and late responses in rat vascular smooth muscle cells. Angiotensin II induced a rapid and transient elevation of inositol trisphosphate intracellular levels, triggered the release of both prostaglandin E2 and prostaglandin I2 (EC50 = 21 +/- 3 and 16 +/- 2 nM, respectively), and, in long-term studies, increased leucine and thymidine incorporation. All angiotensin II effects were antagonized by LR-B/081 and losartan, the reference non-peptide angiotensin AT1-selective receptor antagonist, whereas they were unaffected by PD123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetr ahy dro-1H- imidazo[4,5-c]pyridine carboxylic acid), a non-peptide angiotensin AT2-selective receptor antagonist. LR-B/081 displayed a much higher potency than losartan in inhibiting angiotensin II-induced prostaglandin E2 (IC50 = 0.15 +/- 0.02 and 39 +/- 9 nM, respectively) and prostaglandin I2 release (IC50 = 0.18 +/- 0.04 and 134 +/- 40 nM, respectively) and was also more potent in blocking the increase in protein synthesis (IC50 = 242 +/- 119 nM and 1221 +/- 687 nM, respectively). Moreover, LR-B/081 and losartan blocked the response to angiotensin III but failed to inhibit the prostaglandin release stimulated by vasopressin or the mitogenic effect of serum. LR-B/081 and losartan were devoid of intrinsic properties in the experimental conditions employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II-induced responses in vascular smooth muscle cells: inhibition by non-peptide receptor antagonists. 856 96

We have characterized a specific binding site for angiotensin IV on bovine aortic endothelial cell membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.71; average of two experiments that yielded values of 0.71 and 0.72 nM). The binding site is saturable and relatively abundant with a maximal binding capacity of 0.59 pmol/mg protein (average of two experiments that yielded values of 0.39 and 0.78 pmol/mg of protein). Non-equilibrium kinetic analyses at 37 degree C revealed a calculated Kd of 59 pM (average of two experiments that yielded values of 67 and 50 pM). The binding site displays a high affinity for angiotensin receptors AT1 or AT2. An analysis of specificity showed that the binding site displays a high affinity for angiotensin IV, low affinities for angiotensin II, [Sar1, Val5, Ala8]angiotensin II and does not recognize L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'-(1 H-tetrazole-5-yl)[1,1'-biphenyl]-4-yl)methyl]-3H-imidazo[4, 5-beta]pyridine H2O) and PD 123319 (1-[4-dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl) 4,5,6,7-tetrahydro-1 H-imidazo[4,5-c]pyridine-6-carboxylic acid). A few unrelated hormones (bradykinin, [Arg8] vasopressin, endothelin-1, atrial natriuretic factor, isoproterenol and adrenocorticotropic hormone) were unable to inhibit any 125I-angiotensin IV binding. The affinities of different structural analogues of angiotensin IV revealed that the N-terminal position is critical for receptor recognition and the C-terminal proline is also important. GTP gamma S and polyvinyl sulfate did not affect the binding, suggesting that the receptor is not coupled to a G-protein. The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of 125I-angiotensin IV. Cross-linking of 125I-angiotensin IV to bovine aortic endothelial cell membranes in the presence of disuccinimidyl suberate, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a major band of 186 +/- 12 kDa. The presence in high concentration of this angiotensin binding site on aortic endothelial cells suggest the existence of a novel mechanism involved in the control of vascular tone or vascular permeability.
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PMID:Characterization of a binding site for angiotensin IV on bovine aortic endothelial cells. 856 70

1. In some tissues, a decrease in the number of cell surface receptors and alterations of the receptor coupling have been proposed as possible mechanisms mediating the deleterious effects of bacterial endotoxin in septic shock. 2. The effects of bacterial lipopolysaccharide (Escherichia coli 0111-B4; LPS) on vascular angiotensin II and vasopressin receptors have been examined in cultured aortic smooth muscle cells (SMC) of the rat by use of radioligand binding techniques. 3. In vascular SMC exposed to 1 micrograms ml-1 endotoxin for 24 h, a significant increase in angiotensin II binding was found. The change in [125I]-angiotensin II binding corresponded to an increase in the number of receptors whereas the affinity of the receptors was not affected by LPS. In contrast, no change in [3H]-vasopressin binding was observed. 4. The pharmacological characterization of angiotensin II binding sites in control and LPS-exposed cells demonstrated that LPS induced an increase in the AT1 subtype of the angiotensin II receptors. Receptor coupling as evaluated by measuring total inositol phosphates was not impaired by LPS. 5. The effect of LPS on the angiotensin II receptor was dose-, time- and protein-synthesis dependent and was associated with an increased expression of the receptor gene. 6. The ability of LPS to increase angiotensin II binding in cultured vascular SMC was independent of the endotoxin induction of NO-synthase. 7. These results suggest that, besides inducing factors such as cytokines and NO-synthase, endotoxin may enhance the expression of cell surface receptors. The surprising increase in angiotensin II binding in LPS exposed VSM cells may represent an attempt by the cells to compensate for the decreased vascular responsiveness. It may also result from a non-specific LPS-related induction of genes.
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PMID:Effect of endotoxin on the angiotensin II receptor in cultured vascular smooth muscle cells. 858 Dec 94

The peptide hormones angiotensin II and vasopressin play a major role in water and electrolyte homeostasis. These peptides act on membrane bound receptors, which all belong to the large family of G protein coupled receptors. The receptors for angiotensin II are divided into 2 groups: the AT1 receptors, which are responsible for transducing the majority if not all actions of angiotensin II. The primary structure of this receptor has been identified by molecular cloning of the cDNA in many species and is represented by two isoforms (AT1A and AT1B) in rodent. This receptor is specifically coupled to a G protein of the Gq family, which activates a phospholipase C producing two second messengers involved in protein phosphorylation and calcium mobilization. The sequences or amino-acids involved in the binding site of peptidic agonists or non peptidic antagonists and in receptor activation and G protein coupling have been identified; the AT2 receptor primary sequence has also been identified, but the physiological role and the signaling mechanisms of this receptor are still unknown. The vasopressin receptors can be divided in three classes depending on their pharmacological properties, their tissular distribution and their coupling mechanisms. The primary structure of all 3 types of receptors has been elucidated. The V1a receptor is ubiquitous and transduces the vasoconstrictive effect of vasopressin by activating a phospholipase C, like the AT1 receptors; the V2 receptor is involved in water reabsorption in the kidney and is coupled to a GS protein activating an adenylyl cyclase; the V3 or V1b receptor is expressed in the pituitary, where it regulates the ACTH secretion, via the activation of a phospholipase C. These two family of G protein coupled receptors illustrate the structural and functional diversity of the receptors for peptidic hormones.
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PMID:[Comparative study of the structure and molecular functions of angiotensin II and vasopressin receptors]. 859 Feb 17

We have examined the cAMP-independent regulation of cytosolic calcium concentration in rat Sertoli cells using the effect of vasoactive hormones, known as testicular paracrine regulators operating via the non-cAMP pathway, on cytosolic calcium. Calcium concentrations were estimated with dual excitation fluorimetry, using freshly isolated, fura-2/AM-loaded cells. No increase in the cellular cAMP concentration was detected after stimulation with angiotensin II (AII), vasopressin, PGF2 alpha, or atrial natriuretic peptide. Whereas both AII and vasopressin evoked a rise in cytosolic calcium from a basal level of 81.4 +/- 4 to 142.5 +/- 18 and 154.4 +/- 11 nM, respectively, PGF2 alpha had only a minimal effect (98 +/- 5 nM), and atrial natriuretic peptide no effect (86.6 +/- 9 nM). The effect of AII on calcium was blocked by the the selective AT2, but not by the AT1, receptor antagonist, indicating the selective presence on Sertoli cells of AT2 AII receptor. Similarly, the vasopressin-induced calcium response was blocked by vasopressin V1, but not by V2 receptor antagonist, consistent with the presence of V1 receptor subtype in these cells. Removal of extracellular calcium or blockade of calcium channels did not inhibit the calcium increase due to AII and vasopressin, suggesting the involvement of intracellular calcium. Thapsigargin increased the basal cytosolic calcium concentration to 137 +/- 10 nM. Depletion of intracellular calcium stores with thapsigargin before stimulation with AII or vasopressin abolished both the AII-mediated and the vasopressin-mediated calcium rise in the presence as well as the absence of extracellular calcium, indicating that the increase in calcium is predominantly derived from the thapsigargin-sensitive endoplasmic reticulum. This study indicates that calcium homeostasis of Sertoli cells might also be regulated by cAMP-independent metabolism apart from the well known cAMP-dependent pathway. Furthermore, our findings support the idea that angiotensin and vasopressin might be important paracrine regulators of Sertoli cells functions.
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PMID:Cyclic adenosine 3',5'-monophosphate-independent regulation of cytosolic calcium in Sertoli cells. 864 Dec 16

This study was designed to ascertain whether the extracellular loops of vasopressin/oxytocin receptors bind ligands and, if so, to locate the molecular determinants of this ligand-receptor interaction. Ligand-binding studies were employed using a rat liver V1a vasopressin receptor preparation and both peptide and non-peptide receptor ligands. Synthetic peptides corresponding to defined regions of the extracellular surface of the neurohypophysial hormone receptors recognized radioligands. These receptor mimetics inhibited the binding of radioligands to the V1a receptor with apparent affinities (pKi) ranging from 3.1 to 6.75. The same mimetics had no effects on the binding of angiotensin II to the rat AT1 receptor, indicating specificity for V1a receptor ligands. A mimetic peptide (DITYRFRGPDWL) of the first extracellular loop (ECII) of the V1a vasopressin receptor also inhibited vasopressin-stimulated, but not angiotensin II-stimulated, glycogen phosphorylase in isolated rat hepatocytes. In contrast, scrambled ECII mimetics displayed greatly reduced affinity for vasopressin. In addition, the role of peptide side-chain versus main-chain atoms in the binding of ligands by vasopressin receptors was addressed using retro-inverso peptide mimetics. Our findings indicate a precise orientation of the extracellular receptor surface (particularly the ECII domain) which facilitates the initial 'capture' of both peptide and non-peptide ligands. Moreover, the data indicate that the main-chain atoms of both a major binding-site determinant in the first extracellular loop of the receptor and the neurohypophysial hormones contribute significantly to the ligand-receptor interaction. These findings also suggest that soluble receptor-binding domains have therapeutic potential.
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PMID:Molecular recognition of peptide and non-peptide ligands by the extracellular domains of neurohypophysial hormone receptors. 871 88

1. Male (350-450 g) Long Evans rats were chronically instrumented to permit regional haemodynamics to be monitored in the conscious state. In the first experiment, either saline (0.4 ml h-1) or dexamethasone (3 mg kg-1, 125 micrograms kg-1 h-1) was infused continuously for 24 h, before co-infusion of lipopolysaccharide of (LPS, 150 micrograms kg-1 h-1) for 24 h. Dexamethasone prevented the delayed (5-24 h) fall in mean arterial blood pressure (MAP) and the renal and hindquarters vasodilatation seen with LPS infusion alone, but not the initial (about 2 h) fall in MAP or renal vasodilatation. However, at this dose, dexamethasone itself caused a significant rise in MAP and regional vasoconstrictions. 2. In the second experiment, dexamethasone at a lower dose (12.5 micrograms kg-1 h-1) had only slight pressor and vasoconstrictor effects. However, in its presence, infusion of LPS caused a substantial and progressive rise in MAP (maximum at 8 h, +32 +/- 3 mmHg) together with persistent mesenteric and hindquarters vasoconstriction and a transient renal vasodilatation. 3. In the third experiment, the non-selective endothelin antagonist, SB 209670 (600 micrograms kg-1 h-1), blocked the slight pressor and regional vasoconstrictor effects of the lower dose of dexamethasone. Furthermore, in the presence of dexamethasone and SB 209670, infusion of LPS caused marked, but transient hypotension (nadir at 5 h, -24 +/- 2 mmHg) and renal and mesenteric vasodilatation. 4. At the end of all experimental protocols, sequential administration of the AT1-receptor antagonist, losartan, followed by the V1-receptor antagonist, (+)-(CH2)5-O-Me-Tyr, vasopressin, caused effects indicating a variable involvement of angiotensin and vasopressin in the maintenance of cardiovascular status. 5. Collectively, the results indicate that, in the conscious rat, dexamethasone interacts with vasoconstrictor and vasodilator mechanisms, and hence its influence on the haemodynamic responses to LPS cannot be attributed, simply, to inhibition of the activity of inducible nitric oxide synthase and/or cyclo-oxygenase-2.
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PMID:Effects of dexamethasone and SB 209670 on the regional haemodynamic responses to lipopolysaccharide in conscious rats. 873 87

1. Male, vasopressin-deficient, normotensive (DI/N) and hypertensive (DI/H) rats were chronically instrumented (all surgery under sodium methohexitone anaesthesia) to allow assessment of resting haemodynamic status and responses to antagonism of AT1-receptors (Experiment 1), ET(A-) and ET(B-) receptors (Experiment 2) or adrenoceptors (Experiment 3). 2. Before any treatment, mean arterial blood pressure (MAP) was higher, and hindquarters vascular conductance was consistently lower in all groups of DI/H rats than in DI/N rats. 3. In Experiment 1, losartan (10 mg kg-1 i.v.), an AT1-receptor antagonist, was given 5 h after s.c. injection of saline, (DI/N, n = 8; DI/H, n = 8) or hyperoncotic polyethylene glycol, (DI/N, n = 9; DI/H, n = 9) to induce isosmotic hypovolaemia. In the volume-replete state, losartan caused similar small falls in MAP in the two groups (maximum delta MAP; DI/N, -9 +/- 2; DI/H, -15 +/- 5 mmHg), but the mesenteric and hindquarters vasodilatations were greater in DI/N rats. In the volume-depleted state the effects of losartan were augmented (delta MAP; DI/N, -32 +/- 3; DI/H. -31 +/- 3 mmHg), but its vasodilator effects were still greater in DI/N than in DI/H rats. 4. In Experiment 2, infusion of the ET(A-)ET(B-)receptor antagonist, SB 209670 (600 micrograms kg-1 h-1; DI/N, n = 8; DI/H, n = 9), had haemodynamic effects that were not different from those during saline infusion in DI/N (n = 7) and DI/H rats (n = 8). 5. In Experiment 3, sequential administration of the beta 2-adrenoceptor antagonist, ICI 118551 (0.2 mg kg-1 bolus, 0.1 mg kg-1 h-1 infusion), the alpha 2-adrenoceptor antagonist, idazoxan (0.75 mg kg-1 bolus, 1 mg kg-1 h-1 infusion), and losartan (10 mg kg-1 bolus) had only slight haemodynamic effects in DI/N (n = 8) and DI/H (n = 9) rats. Subsequent administration of the alpha 1-adrenoceptor antagonist, prazosin (0.5 mg kg-1 bolus, 0.8 mg kg-1 h-1 infusion) caused marked hypotension, although MAP was still higher in DI/H (95 +/- 4 mmHg) than in DI/N (75 +/- 4 mmHg) rats. However, in this circumstance there were no significant differences between renal, or mesenteric, or hindquarters vascular conductances in the two groups. 6. The results indicate that the hypertension and hindquarters vasoconstriction in DI/H rats is not dependent on AII or endothelin. Moreover, the relative elevation in MAP in DI/H persists in the presence of antagonism of beta 2, alpha 2- and alpha 1-adrenoceptors, in spite of no significant difference in regional vascular conductances.
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PMID:Regional haemodynamic effects of antagonists of angiotensin II, endothelin and adrenoceptors in conscious, vasopressin-deficient, genetically hypertensive rats. 873 34


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