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

Membrane proteins from isolated, purified ox neurohypophyseal secretory granules were separated by sodium dodecylsulphate (SDS) polyacrylamide gel electrophoresis (PAGE). Using a gel overlay technique, after renaturation procedures, it was demonstrated that 125J calmodulin bound in a Ca2+-dependent way to two protein bands with molecular weights (MW) of 58,000 and 52,000. Binding of small amounts of calmodulin to other protein bands was independent of calcium. No calmodulin binding to granule content proteins could be detected. Treatment of the granules with trypsin prior to separation of membrane proteins removed the Ca2+-dependent binding proteins from the granule membrane. On incubation of granules with [gamma-32P]ATP, protein bands with MW of 52,000 and 45,000 showed a marked phosphorylation activity. The 52,000 band had the same electrophoretic mobility as one of the calmodulin-binding bands. However, no effect of calmodulin on phosphorylation of this band could be demonstrated.
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PMID:Identification of calmodulin-binding proteins on membranes of secretory granules isolated from bovine neurohypophyses. 372 45

Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreatic beta-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.
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PMID:Immunocytochemical demonstration of calmodulin in cells secreting by exocytosis. 389 12

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

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

Vasopressin affects a variety of cell systems. This review is focused on permeability changes induced by vasopressin in tight epithelia such as the collecting duct of the mammalian kidney and the skin and the bladder of anurans. These vasopressin effects are discussed with reference to current concepts and models of the microstructure of the plasma membrane. The transport of three major chemical species--Na, urea and water--is analyzed. In each instance, the hormone appears to activate selective membrane pathways situated at the rat-limiting barrier of the epithelium, i.e., the apical membrane. Available data suggest that two intra-cellular messengers -- cAMP and calcium -- plan a key role in the coupling between stimulus (receptor occupancy) and biological effect (permeability change). The enhancement of Na transport (natriferic effect) depends on the opening and/or the insertion of Na channels, the biophysical and biochemical characteristics of which have been investigated by fluctuation analysis and by means of several chemical blockers of Na transport, particularly the amiloride molecule and its congeners. Likewise, the finding of inhibitors and activators of urea transport, which do not cause any appreciable change in Na or water permeability, led to the notion of selective urea channels or pores. Finally, the enhancement of water transport (hydrosmotic effect) possibly results from the insertion in the apical membrane of water channels already present in vesicular cytoplasmic structures. The restructuring of the apical membrane underlying the transition from a low to a higher state of water permeability is very likely related to the appearance of intramembrane particle aggregates detectable with the freeze-fracture technique in epithelia exposed to vasopressin. The putative water channels (or pores) appear to be so narrow that trans-apical water movement is constrained to single-file diffusion. Recent data also suggest that, in addition to cAMP, microtubules and microfilaments, the calmodulin-Ca complex is a major element in the hydrosmotic effect of vasopressin.
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PMID:The mode of action of vasopressin: membrane microstructure and biological transport. 626 76

The hydro-osmotic response of the toad bladder to antidiuretic hormone and cyclic AMP was inhibited by the methoxyflurane metabolite, fluoride. The osmotic transfer of water in the absence of hormone was unaffected by fluoride as was the hydroosmotic response due to hypertonicity of the serosal bathing media. Osmotic water movements across N-ethylmaleimide-"fixed" vasopressin or cyclic AMP-stimulated bladders were likewise unchanged by fluoride, suggesting that fluoride is exerting an action subsequent to the endogenous formation of cyclic AMP but before the final effector mechanism. Fluoride increased intracellular cyclic AMP concentrations even in the presence of added hormone. Fluoride suppressed calmodulin activity and prevented its activation of phosphodiesterase. Fluoride had no effect on oxygen consumption of toad urinary bladder cells but reduced lactate formation and anerobic metabolism. This decrease in the glycolytic energy source did not contribute to the inhibition of the hormonal response since 2-deoxyglucose was without effect on hormonal mediated osmotic-water flow. It is postulated that the fluoride-induced polyuria after methoxyflurane anesthesia may be due in part to the ability of fluoride to interfere with calcium and calmodulin-initiated processes (other than phosphodiesterase activity) that may occur in the stimulus-reabsorption coupling response of antidiuretic hormone.
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PMID:Fluoride inhibition of the hydro-osmotic response of the toad urinary bladder to antidiuretic hormone. 627 Mar 9

A rabbit liver cAMP-independent glycogen synthase kinase has been purified 4500-fold to a specific activity of 2.23 mumol of 32P incorporated per min per mg of protein using ion exchange chromatography on DEAE-Sephacel and phosphocellulose, gel filtration chromatography on Sepharose 6B, and affinity chromatography on calmodulin-Sepharose. This synthase kinase, which was completely dependent on the presence of calmodulin (apparent K0.5 = 0.1 microM) and calcium for activity, also catalyzed the phosphorylation of purified smooth muscle myosin light chain but not of smooth muscle myosin. Using 0.5 mM ATP, a maximal rate of phosphorylation of glycogen synthase was achieved in the presence of 10 mM magnesium acetate with a pH optimum of 7.8. Gel filtration experiments indicated a Stokes radius of about 70 A and sucrose density gradient centrifugation data gave a sedimentation coefficient of 10.6 S. A molecular weight of approximately 300,000 was calculated. A definitive subunit structure was not determined, but major bands observed after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate corresponded to a doublet at 50,000 to 53,000. The calmodulin-dependent glycogen synthase kinase incorporated about 1 mol of 32P per mol of synthase subunit into sites 2 and 1b associated with a decrease in the synthase activity ratio from 0.8 to about 0.4. The calmodulin-dependent glycogen synthase kinase may mediate the effects of alpha-adrenergic agonists, vasopressin, and/or angiotensin II on glycogen synthase in liver.
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PMID:Purification and characterization of rabbit liver calmodulin-dependent glycogen synthase kinase. 629 43

Microtubules, microfilaments, and intermediate filaments were found to be associated with the cytoplasmic face of the plasma membrane and even localized on the cell surface following "perturbation" of the plasma membrane. Several hormones interacting with their surface receptors have an effect on the assembly, organization, and orientation of the cytoskeletal system thus inducing changes in cell morphology, motility and aggregation. The cytoskeletal system is probably responsible for the lateral and vertical mobility of plasma membrane receptors and for the efficient coupling of GTP-binding protein to the adenylate cyclase moiety. It is suggested that the cytoskeletal system may be involved in hormone-induced desensitization. The activity of cyclic nucleotide phosphodiesterase and protein kinase is modulated by Ca2+-calmodulin. These enzymes are associated with intermediate filaments and with microtubules which may control their activity and induce nuclear translocation of protein kinase. Stimulation of steroidogenesis by ACTH and LH, enhancement of H2O transport by vasopressin, elevation of the rate of amino acid and glucose transport by insulin, release of pancreatic insulin by glucose, and pituitary hormones by their respective hypothalamic releasing hormones, are only examples of a variety of hormonal responses that may be regulated by the cytoskeletal system. It is obvious that much more experimental study should be done to establish the role of the cytoskeletal system in hormonal action. I do hope this review will stimulate further ideas and experiments which might eventually lead to a better understanding of the role of the cytoskeletal system in the control of adenylate cyclase-cAMP system stimulated by hormones.
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PMID:Role of cytoskeletal organization in the regulation of adenylate cyclase-cyclic adenosine monophosphate by hormones. 629 17

1. The informational role of cytosolic Ca2+ appears to be mediated by a ubiquitous protein--calmodulin--in most cell systems. 2. Evidence has been accumulating that not only cAMP, but also Ca2+, behaves as an intracellular messenger in the stimulation of water transport by vasopressin (hydrosmotic effect). 3. To examine whether calmodulin plays a role in the hydrosmotic effect of vasopressin, we used a specific antagonist of calmodulin--trifluoperazine--and looked at its effects on water transport in the urinary bladder of toads Bufo marinus. 4. The results showed that trifluoperazine, at micromolar concentrations, blocked the hydrosmotic effects of vasopressin or cAMP, thus indicating a post-cAMP site of action. 5. Two other psychotropic drugs--amitriptyline and harmaline--had similar effects, but higher concentrations were required to induce the same degree of inhibition of water flow. 6. Calmodulin was detected in the membrane and in the cytosolic fractions of isolated epithelial cells of toad bladder by means of the phosphodiesterase test. The content of both fractions was similar to that found in bovine brain. 7. The results suggest that calmodulin plays a regulatory role in the hydrosmotic action of vasopressin by possibly interacting with proteins associated with microfilaments and/or microtubules.
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PMID:Evidence for a role of calmodulin in the hydrosmotic action of vasopressin in toad bladder. 630 Mar 78

Vasopressin elicited a dose-dependent inhibition of glucagon-induced cAMP accumulation in isolated hepatocytes. This response was not diminished by incubation of cells with the calmodulin antagonists trifluoperazine or chlorpromazine and was only slightly reduced in Ca2+-depleted hepatocytes. Half-maximal inhibition of cAMP accumulation occurred at 8 X 10(-11) M vasopressin, a dose which does not increase cytosolic Ca2+ in hepatocytes. Direct activation of adenylate cyclase by forskolin was significantly inhibited by vasopressin in Ca2+-depleted cells. It is concluded that inhibition of hormone-induced cAMP accumulation by vasopressin in liver is not dependent on cellular Ca2+ mobilisation but may involve direct inhibition of adenylate cyclase.
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PMID:Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin. 631 90


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