UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma membrane of the bovine renal collecting duct epithelial cell has been resolved into its apical (luminal) and basal-lateral (contraluminal) components by free flow electrophoresis. The contraluminal, but not the luminal, membrane was found to contain antidiuretic hormone-sensitive adenylate cyclase. The luminal membrane was found to contain a cyclic 3':5'-adenosine monophosphate-sensitive self-phosphorylating system consisting of a membrane-bound protein kinase and its membrane-bound substrate(s); this intrinsic protein kinase was not present in the contraluminal membrane. These findings provide direct evidence that the initiating steps in the action of antidiuretic hormone on the kidney take place at the contraluminal pole of the hormonesensitive target cell and that the late or terminal steps occur at the luminal pole, where they involve an alteration in the level of membrane phosphorylation.
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PMID:Target cell polarity and membrane phosphorylation in relation to the mechanism of action of antidiuretic hormone. 436 61

The mechanism of actions of glucagon, alpha- and beta-adrenergic agonists, vasopressin and angiotensin II in the liver proposed in this article are summarized in Fig. 8. The actions of glucagon and beta-adrenergic agonists in liver can be entirely ascribed to their interaction with specific plasma membrane receptors which activate adenylate cyclase leading to the intracellular accumulation of cAMP and activation of cAMP-dependent protein kinase. This enzyme phosphorylates phosphorylase b kinase, glycogen synthase, L-type pyruvate kinase, and other liver proteins resulting in alterations in their activities which can account for several of the known hepatic responses to glucagon. There is no clear evidence that Ca2+ ions are involved in the hepatic actions of this hormone. Glucocorticoids, but not thyroid hormones, are required for normal responsiveness of the liver to glucagon. The steroids do not modify cAMP accumulation or cAMP-dependent protein kinase activation, but may act by modulating the action of the kinase on its substrates. Glucocorticoids and thyroid hormones decrease beta-adrenergic responses in the liver apparently by decreasing the number of beta-receptors. Insulin inhibits the actions of physiological concentrations of glucagon by decreasing cAMP accumulation: its mechanism of action is unknown. The actions of alpha-adrenergic agonists, vasopressin and angiotensin II on the liver resemble those of glucagon, but do not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. These agents appear to act by increasing cytosolic Ca2+ thus altering the activities of Ca2+-sensitive enzymes such as phosphorylase b kinase and calmodulin-dependent glycogen synthase kinase. Their receptors appear to be located exclusively on the plasma membrane and a major mechanism by which they raise cytosolic Ca2+ is by inducing the release of this cation from mitochondria. These considerations imply the existence of an intracellular messenger(s) for these agents which is generated at the plasma membrane in response to receptor activation and exerts effects on mitochondria or perhaps other intracellular structures. Glucocorticoids and thyroid hormones increase alpha-adrenergic responses in the liver apparently by increasing the number of alpha-receptors. Insulin inhibits the responses of the liver to alpha-agonists, but not to vasopressin or angiotensin II.
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PMID:Mechanisms of hormonal regulation of liver metabolism. 611 89

2-Mercapto-1-(beta-4-pyridethyl) benzimidazole (MPB) was originally introduced as a reversible inhibitor of RNA synthesis, but subsequent findings made this suggestion doubtful. We examined the effect of MPB on active sodium transport, measured as short-circuit current (scc), across the isolated urinary bladder of the toad (Bufo marinus). The drug caused a rapid, dose-dependent inhibition of baseline scc; 25 micrograms/ml MPB reduced it by 70%. Sensitivity to MPB was the same in the presence and absence of metabolizable substrate. The transport stimulation by aldosterone (7 X 10(-8)M) was abolished entirely when MPB was introduced 30 min before the hormone. In bladders incubated with MPB with or without aldosterone, removal of both agents resulted in a rise in scc, which was more rapid in the aldosterone-pretreated hemibladders; a significant difference was observed after 30 min. This suggests that MPB inhibited transport at a site distal to messenger RNA accumulation. The effect of 3 hr of pretreatment with MPB on the response of the bladders to antidiuretic hormone (ADH, 20 mU) and cyclic AMP (cAMP, 10 mM) was then examined. The absolute increment in scc due to these agents was the same as in the absence of MPB, though the baseline was much reduced by the drug. After challenging MPB-pretreated bladders with theophylline (22.5 mM), sodium transport rose continuously for 90 min, in contrast to the small, short-lived rise in the absence of MPB. It is proposed that, in the toad bladder, MPB may: (1) inhibit cAMP-dependent protein kinase, as found by us in other tissues; and (2) counteract the accumulation of a transport inhibitor, possibly calcium or cyclic GMP, in tissues treated with endogenous or exogenous cAMP.
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PMID:2-Mercapto-1-(beta-4-pyridethyl) benzimidazole inhibition of basal and aldosterone-stimulated sodium transport but prolongation of the transient theophylline-induced stimulation in the toad bladder. 619 73

Angiotensin II, catecholamines, and vasopressin can stimulate the phosphorylation of 10 hepatic cytosolic proteins via a Ca2+-linked, cyclic AMP-independent mechanism. To explore the role of known Ca2+-sensitive protein kinases in this response, [32P]PO4(3-)-labeled hepatocytes were stimulated with various agonists, the cytoplasmic proteins were separated on two-dimensional gels, and the resulting autoradiographs were computer analyzed. The role of phosphorylase kinase was examined using hepatocytes from gsd/gsd rats which are deficient in this enzyme. The phosphorylation state of phosphorylase was not increased by glucagon, angiotensin II, or vasopressin in hepatocytes from the gsd/gsd animals. The phosphorylation state of all other substrates was changed by glucagon or the Ca2+-linked hormones to the same extent in gsd/gsd hepatocytes as in normal Wistar controls, suggesting that phosphorylase kinase plays a restricted role in the hormone response. The role of the Ca2+- and phospholipid-sensitive protein kinase (protein kinase C) was examined by stimulating hepatocytes with phorbol esters which are thought to activate protein kinase C by substituting for diacylglycerol. Phorbol esters increased the phosphorylation state of 3 of the 10 substrates affected by angiotensin II or vasopressin, but did not stimulate Ca2+ fluxes in hepatocytes. Treatment of hepatocytes with the Ca2+ ionophore A23187 mimicked the effect of the Ca2+-linked hormones on the phosphorylation of the other 7 substrates. The results demonstrate that at least three Ca2+-sensitive protein kinases are involved in the response of hepatocytes to Ca2+-linked hormones. Since these kinases can be activated independently by phorbol esters or A23187, the results imply that hormones such as vasopressin generate two intracellular messengers, diacylglycerol and Ca2+ ion.
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PMID:Evidence for the role of phosphorylase kinase, protein kinase C, and other Ca2+-sensitive protein kinases in the response of hepatocytes to angiotensin II and vasopressin. 623 Mar 57

The effect of vasopressin on the toad urinary bladder has been shown to be mediated by cyclic AMP. It has been assumed that, as demonstrated for other systems, this involves activation of cyclic AMP-dependent protein kinase. In order to test this hypothesis we investigated the effect of vasopressin on cyclic AMP-dependent protein kinases in epithelial cells of toad bladders. About 80% of protein kinase activity and cyclic AMP-binding capacity was found to be in the cytosol. DEAE-cellulose chromatography showed a pattern of 15--20% type I and 80--85% type II cyclic AMP-dependent protein kinase. Cytosolic kinase was activated 3--4-fold by cyclic AMP with half-maximal activation at 5 . 10(-8) M. Similarly, half-maximal binding of cyclic AMP occurred at 7 . 10(-8) M. Incubation of toad bladders in Ringer's solution containing 0.1 mM 3-isobutyl-1-methylxanthine, prior to homogenization and assay, showed stable cyclic AMP-binding capacity and protein kinase ratio --cyclic AMP/+cyclic AMP. Exposure of bladders to 10 mU/ml of vasopressin for 10 min caused intracellular activation of protein kinase and decrease in cyclic AMP-binding capacity that were maintained for at least 30 min. Incubation of bladders with increasing concentrations of vasopressin (0.5--100 mU/ml) resulted in a discrepancy between a progressive increase in cyclic AMP levels and a levelling off at 10 mU/ml of vasopressin for the changes in protein kinase ratio and cyclic AMP-binding capacity. The increase in kinase ratio was due to higher activity in the absence of exogenous cyclic AMP and was fully inhibitable by a specific protein kinase inhibitor. Using Sephadex G-25-CM50 column chromatography for separation of holoenzyme and free catalytic subunit we demonstrated that the activation of protein kinase in the vasopressin-treated bladders is due to intracellular dissociation of the kinase. These results show that the effect of vasopressin on the toad bladder involves activation of a cytosolic cyclic AMP-dependent protein kinase. The time course and the dose-response curve of the kinase activation closely parallel vasopressin's effect on osmotic water flow.
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PMID:Effect of vasopressin on cyclic AMP-dependent protein kinase in toad urinary bladder. 624 97

We have previously demonstrated that a cultured porcine kidney cell, LLC-PK(1), maintains the characteristics of a polar renal epithelial cell in culture, and responds to salmon calcitonin and [arginine]vasopressin by increasing cyclic AMP content. To demonstrate the usefulness of this cell line as a model for the study of the biochemical events distal to cyclic AMP production, the activation of cyclic AMP-dependent protein kinase was examined. Intact cells in monolayer demonstrated progressive increases in cyclic AMP content and activation of protein kinase in response to [arginine]vasopressin (2-200nm) and salmon calcitonin (0.03-30nm) with both hormones fully activating the enzyme at a cell cyclic AMP content of 35pmol/mg of protein. Of the total cyclic AMP-dependent protein kinase activity, 80% was found in the 27000g supernatant fraction of sonicated cell material, and this soluble protein kinase could be fully activated by hormone. Conversely, the 27000g pellet contained a significant proportion of cyclic AMP-independent protein kinase and only 20% of total cell cyclic AMP-dependent protein kinase; the latter showed little response to hormone. On the basis of DEAE-cellulose chromatography, type II protein kinase was the predominant isoenzyme in both soluble and particulate fractions of the LLC-PK(1) cells and the soluble fractions of rat and guinea-pig renal medulla. Thus, the LLC-PK(1) cell line can serve as a model for hormonal modulation of protein kinase and as a potential source for defining the endogenous substrates for these enzymes.
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PMID:Modulation of cyclic AMP-dependent protein kinase by vasopressin and calcitonin in cultured porcine renal LLC-PK1 cells. 624 60

Vasopressin stimulates osmotic water flow and urea permeability in the toad urinary bladder via separate cAMP-responsive mechanisms. Hydrazine (10--20 MM), added to the bladder's serosal bath, reversibly enhanced the effect of both low and saturating levels of vasopressin on osmotic water flow, without increasing urea permeability. A small increase in basal water flow was also observed. Cyclic AMP-stimulated water flow was not altered by hydrazine, but hydrazine enhanced the effect of both 8-bromo-cyclic AMP and methylisobutylxantine. Hydrazine increased luminal membrane aggregate frequency in vasopressin-treated tissues examined by freeze-fracture electron microscopy. Hydrazine increased both basal and vasopressin-stimulated adenylate cyclase activity. We could measure no effect of hydrazine on cAMP content; however hydrazine did increase the protein kinase activity ratio (-cAMP/+cAMP) in vasopressin-treated tissues, suggesting that the kinase activity ratio is more sensitive than cAMP content as an index of cAMP-related function in the bladder. Further strengthening the relationship between kinase activation and water flow, we found that methohexital, an inhibitor of vasopressin-stimulated water flow and adenylate cyclase, also decreased the kinase activity ratio in the presence of vasopressin. These studies link closely the role of cAMP-dependent kinase and luminal membrane aggregates to the specific mediation of vasopressin-stimulated water flow in the bladder.
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PMID:Effect of hydrazine on transport on toad urinary bladder. 625 84

Amrinone is a new noncatechol, nonglycoside agent with cardiotonic and vasodilator properties. This paper examines the effects of amrinone in the toad urinary bladder, a tissue whose function may be altered by many factors which also change cardiovascular activity. Amrinone enhanced the effect of vasopressin and cyclic AMP on water and urea permeabilities, as well as the effect of vasopressin on sodium transport. Consistent with these actions, amrinone inhibited cyclic AMP phosphodiesterase activity in epithelial homogenates and increased both cyclic AMP content and the protein kinase activity ratio measured in intact epithelial cells. The inhibitory effect of amrinone on phosphodiesterase may be relevant to its cardiostimulatory and vasodilator activities.
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PMID:The effects of amrinone on transport and cyclic AMP metabolism in toad urinary bladder. 625 81

Perfusion of livers from fed rats with medium containing glucagon (2 x 10(-10) or 1 x 10(-8) M) resulted in both time- and concentration-dependent inactivation of glycogen synthase phosphatase. Expected changes occurred in cAMP, cAMP-dependent protein kinase, glycogen synthase, and glycogen phosphorylase. The effect of glucagon on synthase phosphatase was partially reversed by simultaneous addition of insulin (4 x 10(-8) M), an effect paralleled by a decrease in cAMP. Addition of arginine vasopressin (10 milliunits/ml) resulted in a similar inactivation of synthase phosphatase and activation of phosphorylase, but independent of any changes in cAMP or its kinase. Phosphorylase phosphatase activity was unaffected by any of these hormones. Synthase phosphatase activity, measured as the ability of a crude homogenate to catalyze the conversion of purified rat liver synthase D to the I form, was no longer inhibited by glucagon or vasopressin when phosphorylase antiserum was added to the phosphatase assay mixture in sufficient quantity to inhibit 90-95% of the phosphorylase a activity. These data support the following conclusions: 1) hepatic glycogen synthase phosphatase activity is acutely modulated by hormones, 2) hepatic glycogen synthase phosphatase and phosphorylase phosphatase are regulated differently, 3) the hormone-mediated changes in synthase phosphatase cannot be explained by an alteration of the synthase D molecule affecting its behavior as a substrate, and 4) glycogen synthase phosphatase activity is at least partially controlled by the level of phosphorylase a.
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PMID:Hormonal regulation of hepatic glycogen synthase phosphatase. 625 45

Calcium ion plays a major regulatory role in many hormone-stimulated systems. To determine the site of calcium's action in the toad urinary bladder, we examined the effect of trifluoperazine, a compound that binds specifically to the calcium binding protein, calmodulin, and thereby prevents activation of enzymes by the calcium- calmodulin complex. 10 microM trifluoperazine inhibited vasopressin stimulation of water flow, but did not alter vasopressin's effects on urea permeability or short-circuit current. Trifluoperazine also blocked stimulation of water flow by cyclic AMP and methylisobutylxanthine, implying a "postcyclic AMP" site of action. Consistent with these results, trifluoperazine did not decrease epithelial cyclic AMP content or the cyclic AMP-dependent protein kinase activity ratio. Assay of bladder epithelial supernate demonstrated calmodulin-like activity of 1.5 U/microgram protein. Morphologic studies of vasopressin-treated bladders revealed that trifluoperazine did not alter the volume density of cytoplasmic microtubules or significantly decrease the number of fusions between cytoplasmic, aggregate-containing, elongated vesicles and the luminal membrane. Nonetheless, the frequency of luminal membrane aggregates, structures that correlate well with luminal membrane water permeability, was decreased by greater than 50%. Thus, trifluoperazine appears to inhibit the movement of intramembranous particle aggregates from the fused intracellular membranes to the luminal membrane, perhaps by blocking an effect of calcium on microfilament function.
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PMID:Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability. 625 6

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