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)

[Arg8]-vasopressin (AVP) is both a potent vasoconstrictor and a mitogen for vascular smooth muscle cells. AVP binds to a single class of receptors (V1a) in the A7r5 rat aortic smooth muscle cell line (Kd approximately 2 nmol/L). Stimulation of these cells with AVP results in an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) by releasing intracellular Ca2+ stores and increasing Ca2+ influx; the EC50 for these effects is approximately 5 nmol/L. AVP has recently been reported to stimulate arachidonic acid release in primary cultures of rat aortic smooth muscle over a much lower concentration range (EC50 approximately 0.05 nmol/L). The present study examined the effects of varying concentrations of AVP on spontaneous Ca2+ spiking activity in fura 2-loaded A7r5 cells. Frequency of CA2+ spiking increased with increasing [AVP] in the range of 10 to 500 pmol/L. Higher concentrations of AVP inhibited spiking but elicited the characteristic [Ca2+]i changes ascribed to the release of Ca2+ stores and increased Ca2+ entry. The effects of both low and high concentrations of AVP were inhibited by [1-(beta-mercapto-beta,beta,-pentamethylenepropionic acid),2-0-methyltyrosine]arginine vasopressin, a selective V1a vasopressin antagonist. Nimodipine (50 nmol/L), a blocker of L-type voltage-sensitive Ca2+ channels, abolished the Ca(2+)-spiking activity without inhibiting a maximal [Ca2+]i response to AVP (1 mumol/L). AVP-stimulated Ca2+ spiking, but not release of intracellular Ca2+ stores, was also abolished by ONO-RS-082 (1 mumol/L), an inhibitor of phospholipase A2. These results suggest that occupation of a small fraction of V1a vasopressin receptors by AVP results in stimulation of phospholipase A2 and leads to increased Ca(2+)-spiking activity. This effect may be important for fine tuning of vascular tone, whereas maximal stimulation by AVP (full receptor occupancy) may be required for more vigorous or sustained vasoconstriction or mitogenesis.
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PMID:Vasopressin stimulates Ca2+ spiking activity in A7r5 vascular smooth muscle cells via activation of phospholipase A2. 862 Jun 1

[Arg8]vasopressin (AVP), through its V1 receptor coupled to GTP-binding proteins, and aluminum fluoride (AlF4-), which directly activates GTP-binding proteins, induced the release of [3H]arachidonate from prelabeled A7r5 vascular smooth muscle-like cells. Using fura-2-loaded cells, we observed that the release induced by AVP occurred concurrently with calcium (Ca2+) mobilization from internal stores and entry of external Ca2+, whereas AlF4(-)-dependent arachidonate release was much slower and was not accompanied by intracellular Ca2+ mobilization. Arachidonate transfer from phosphatidylcholine to phosphatidylethanolamine was an early event for both agonists, but phosphatidylinositol hydrolysis was an early event for AVP-stimulated cells and a late event for cells triggered with AlF4-. In addition, phospholipase inhibitors had no effect on arachidonate release induced by AlF4-. We investigated the enzymatic pathways involved in the releases of arachidonate, which occur in such different ways. Phospholipase A2 activities were assayed in a cell-free system with various substrates, which made it possible to differentiate between cytosolic, secretory and Ca2(+)-independent phospholipases A2. The specific activities were in the order alkenyl-AA-GPE > acyl-AA-GPE > acyl-AA-GPC in the presence of Ca2+. No significant activity was observed in the presence of Ca2+ chelators and when dipalmitoyl-glycerophosphocholine was used as a substrate. Phospholipase A2 activities did not change in homogenates from stimulated cells related to control cells. However, phospholipase A2 activity increased in membrane fractions from AVP-stimulated cells. Imunodetected phosphorylated and unphosphorylated forms of cytosolic phospholipase A2 (cPLA2) also clearly increased in the membrane fractions of AVP-stimulated cells, and only the unphosphorylated form of cPLA2 was present in AlF4(-)-triggered cells. We conclude that phospholipase C and translocation of cPLA2 can account for arachidonate release with AVP stimulation, whereas neither phospholipase C nor any phospholipase A2 activity appears to be implicated in AlF4(-)-dependent arachidonate release.
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PMID:Phospholipase A2-dependent and -independent pathways of arachidonate release from vascular smooth muscle cells. 906 36

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

Ca2+ influx into cells in response to stimulation of various receptors was studied with Swiss 3T3 fibroblasts. The mechanisms involved were found to be so diverse that they were classified into four groups, Type I to IV. Type-I influx occurred, via pertussis toxin-susceptible G-proteins, immediately after internal Ca2+ mobilization by bradykinin, thrombin, endothelin, vasopressin or angiotensin II. Type-II influx induced by bombesin differed from Type I in its insusceptibility to pertussis toxin treatment. Ca2+ influx induced by prostaglandin E1, referred to as Type-III influx, was unique in that phospholipase C was apparently not activated without extracellular Ca2+, strongly suggesting that the Ca2+ influx preceded and was responsible for InsP3 generation and internal Ca2+ mobilization. More Ca2+ entered the cells more slowly via the Type-IV route opened by platelet-derived and other growth factors. These types of Ca2+ influx could be differentiated by their different susceptibilities to protein kinase C maximally activated by 1 h of exposure of cells to PMA, which inhibited phospholipase Cbeta coupled to receptors involved in Type-I and -II influx but did not inhibit growth-factor-receptor-coupled phospholipase Cgamma. Type-I and -II Ca2+ influxes, together with store-operated influx induced by thapsigargin, were not directly inhibited by exposure of cells to PMA, but Type-III and -IV influxes were completely inhibited. In addition, stimulation of receptors involved in Type-I and -IV Ca2+ influx, but not Type-II and -III influx, led to phospholipase A2 activation in the presence of extracellular Ca2+. Inhibition of Type-I and -IV Ca2+ influxes by their respective inhibitors, diltiazem and nifedipine, resulted in abolition of phospholipase A2 activation induced by the respective receptor agonists, in agreement with the notion that Ca2+ influx via these routes is responsible for receptor-mediated phospholipase A2 activation.
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PMID:Differential routes of Ca2+ influx in Swiss 3T3 fibroblasts in response to receptor stimulation. 940 82

The presence of nitric oxide synthase (NOS) in hypothalamic structures which control the activity of the hypothalamic-pituitary-adrenal (HPA) axis suggests a role for NO in regulation of ACTH and corticosterone secretion. We investigated the involvement of NO in the corticosterone secretion induced by vasopressin (AVP), a potent coregulator of the HPA activity. AVP injected i.p. was, on a molar basis, considerably more potent than administered intracerebroventricularly in inducing corticosterone secretion. This finding suggests a preferential action of AVP on pituitary corticotrop receptors, but not on central structures involved in stimulation of the HPA axis. Dexamethasone given before AVP totally abolished the AVP-elicited corticosterone response by a feedback mechanism and/or inhibition of the phospholipase A2 activity and prostaglandin synthesis. Pretreatment with the NOS inhibitors L-NAME and L-NNA augmented significantly and to a similar extent the corticosterone response to AVP administered both systemically and centrally and L-NNA was found to be more potent in this respect. Pretreatment with L-arginine markedly reduced the AVP-induced corticosterone response. These results suggest that endogenous nitric oxide is significantly involved in the AVP-elicited corticosterone secretion and NO-induced alterations in the prostaglandin synthesis may participate in this action.
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PMID:Role of nitric oxide in the vasopressin-induced corticosterone secretion in rats. 944 26

The amyloid protein precursor (APP) can be processed via several alternative processing pathways. Alpha-secretase processing by cleavage within the amyloid beta-peptide domain of APP is highly regulated by several external and internal signals including G protein-coupled receptors, protein kinase C and phospholipase A2. In order to demonstrate that G protein-coupled neuropeptide receptors for bradykinin and vasopressin can increase alpha-secretase processing of APP, we stimulated endogenously expressed bradykinin or vasopressin receptors in cell culture with the neuropeptides and measured the secreted ectodomain (APPs) in the conditioned media. Both bradykinin and vasopressin rapidly increased phosphatidylinositol (PI) turnover in PC-12 and in NRK-49F cells, indicating that these cell lines constitutively expressed functional PI-linked receptors for these neuropeptides. Both bradykinin and vasopressin readily stimulated APPs secretion. Increased APPs secretion was concentration-dependent and saturable, and it was blocked by receptor antagonists indicating specific receptor interaction of the peptides. The bradykinin-induced increase in APPs secretion in PC-12 cells was mediated by protein kinase C (PKC), whereas vasopressin receptors in NRK-49F cells were coupled to APP processing by PKC-independent signalling pathways. Our data show that neuropeptides can modulate APP processing in cell culture. In as much as increased alpha-secretase processing is associated with decreased formation of A beta(1-40), a major constituent of amyloid plaques, our findings suggest a possible role for modulating neuropeptide receptors as a strategy for altering amyloid metabolism in Alzheimer's disease brain.
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PMID:Vasopressin and bradykinin regulate secretory processing of the amyloid protein precursor of Alzheimer's disease. 956 21

The effect of activation of the Ca2+-sensing receptor on net Cl flux (JCl) has been investigated on microperfused cortical (C) thick ascending limb (TAL) from rat kidney. Increasing bath Ca2+ from 0.5 to 3 mM or adding 200 microM of the specific Ca2+-sensing receptor agonist neomycin reduced basal as well as antidiuretic hormone (ADH)-stimulated JCl by 27.7 +/- 5.0% and 25.9 +/- 4.1%, respectively. JCl remained unchanged in time control tubules. The effect of neomycin/Ca2+ on JCl was blocked by two protein kinase A inhibitors, H-9 or H-89, but not by a protein kinase C inhibitor, GF-109203X, regardless of whether ADH was present or not. Moreover, H-89 decreased basal JCl and prevented a further effect of 3 mM Ca2+. When JCl was increased by 8-bromo-cAMP plus IBMX, no effect of 3 mM Ca2+ was observed. Inhibitors of phospholipase A2 and cytochrome P-450 monooxygenase failed to modify the effect of 3 mM Ca2+, although these agents dampened significantly the inhibitory effect of bradykinin on medullary TAL. We conclude that extracellular Ca2+ decreases basal and ADH-stimulated Cl reabsorption in CTAL by inhibiting the cAMP pathway, independently of protein kinase C or phospholipase A2 stimulation.
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PMID:Extracellular Ca2+ decreases chloride reabsorption in rat CTAL by inhibiting cAMP pathway. 969 Oct 8

Physiological concentrations of [Arg(8)]vasopressin (AVP; 10-500 pM) stimulate oscillations of cytosolic free Ca2+ concentration (Ca2+ spikes) in A7r5 vascular smooth muscle cells. We previously reported that this effect of AVP was blocked by a putative phospholipase A2 (PLA2) inhibitor, ONO-RS-082 (5 microM). In the present study, the products of PLA2, arachidonic acid (AA), and lysophospholipids were found to be ineffective in stimulating Ca2+ spiking, and inhibitors of AA metabolism did not prevent AVP-stimulated Ca2+ spiking. Thin layer chromatography was used to monitor the release of AA and phosphatidic acid (PA), which are the products of PLA2 and phospholipase D (PLD), respectively. AVP (100 pM) stimulated both AA and PA formation, but only PA formation was inhibited by ONO-RS-082 (5 microM). Exogenous PLD (type VII; 2.5 U/ml) stimulated Ca2+ spiking equivalent to the effect of 100 pM AVP. AVP stimulated transphosphatidylation of 1-butanol (a PLD-catalyzed reaction) but not 2-butanol, and 1-butanol (but not 2-butanol) completely prevented AVP-stimulated Ca2+ spiking. Protein kinase C (PKC) inhibition, which completely prevents AVP-stimulated Ca2+ spiking, did not inhibit AVP-stimulated phosphatidylbutanol formation. These results suggest that AVP-stimulated Ca2+ spiking depends on activation of PLD rather than PLA2 and that PKC activation may be downstream of PLD in the signaling cascade.
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PMID:Vasopressin-stimulated Ca2+ spiking in vascular smooth muscle cells involves phospholipase D. 1135 22

We have previously shown that myogenesis induction by Arg8-vasopressin (AVP) in L6 rat myoblasts involves a sustained stimulation of type 4 cAMP-phosphodiesterase. In this model, we observed that a transient cAMP generation occurs in the minutes following AVP addition. Evidence suggests that cAMP generation is due to the prostaglandins produced in response to AVP binding to V1a receptors and subsequent activation of phospholipase A2. The early cAMP increase was effective in activating cAMP-dependent protein kinase (PKA) and increasing phosphorylation of CREB transcription factor. Inhibition of PKA by compound H89 prior to AVP addition led to a significant reduction of expression of the differentiation marker creatine kinase, whereas H89 added 1-5 h after AVP had no significant effect. Furthermore, PKA inhibition 24 h after the beginning of AVP treatment potentiated differentiation. This shows that both an early activation and a later down-regulation of the cAMP pathway are required for AVP induction of myogenesis. Because phosphodiesterase PDE4D3 overexpressed in L6 cells lost its ability to potentiate AVP-induced differentiation when mutated and rendered insensitive to PKA phosphorylation and activation, we hypothesize that the early cAMP increase is required to trigger the down-regulation of cAMP pathway through stimulation of phosphodiesterase.
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PMID:A bimodal modulation of the cAMP pathway is involved in the control of myogenic differentiation in l6 cells. 1450 85

Recently, we reported that intracerebroventricularly (i.c.v.) administered arginine-vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by brain thromboxane A2-mediated mechanisms in rats. These results suggest the involvement of brain arachidonic acid in the vasopressin-induced activation of the central adrenomedullary outflow. Arachidonic acid is released mainly by two pathways: phospholipase A2 (PLA2)-dependent pathway; phospholipase C (PLC)- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we attempted to identify which pathway is involved in the vasopressin-induced release of both catecholamines from adrenal medulla using urethane-anesthetized rats. Vasopressin (0.2 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was dose-dependently reduced by neomycin [0.28 and 0.55 micromol (250 and 500 microg)/animal, i.c.v.] and 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) [5 and 10 nmol (2.3 and 4.6 microg)/animal, i.c.v.] (inhibitors of PLC), and also by 1,6-bis(cyclohexyloximinocarbonylamino)hexane (RHC-80267) [1.3 and 2.6 micromol (500 and 1000 microg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 and 2.2 micromol (500 and 1000 microg)/animal, i.c.v.] (an inhibitor of PLA2) was largely ineffective on the vasopressin-induced elevation of plasma catecholamines. These results suggest that vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by the brain PLC- and diacylglycerol lipase-dependent mechanisms in rats.
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PMID:Brain phospholipase C-diacylglycerol lipase pathway is involved in vasopressin-induced release of noradrenaline and adrenaline from adrenal medulla in rats. 1536 56


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