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)

It has been demonstrated previously that a high concentration of potassium in the serosal bathing medium (5-21.5 mM) potentiates the increase in short-circuit current caused by vasopressin or exogenous cyclic AMP. The same concentration of potassium in the bathing medium inhibited the increase in short-circuit current caused by theophylline. The increases in osmotic water permeability caused by vasopressin or cyclic AMP were unaffected by a serosal potassium concentration of 21.5 mM. The increase in osmotic water permeability caused by theophylline was inhibited by 21.5 mM potassium. The concentration of cyclic AMP in either intact total bladder or isolated toad bladder cells was increased two- or three-fold by theophylline. Increasing the concentration of potassium to 21.5 mM did not alter cyclic AMP concentration in either the absence of presence of theophylline. One interpretation of these results is that theophylline increases osmotic water flow and short-circuit current by a mechanism other than by inhibition of cyclic nucleotide phosphodiesterase.
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PMID:Effects of high potassium concentration on theophylline responses of toad bladder. 19 Aug 97

In experiments on frog urinary bladder the mechanisms behind the gradual development of a hydroosmotic reaction to antidiuretic hormone (ADH) were investigated. It was suggested that the velocity of hydroosmotic reaction may be limited by (a) formation and insertion of particle aggregates into the apical membrane or (b) by velocity of cAMP formation. The urinary bladders were exposed to 23 nM ADH for different times (from 1 to 20 min) and water flow was measured over a period of 40 min. It was found that the value of the full hydroosmotic response increased progressively with the time of exposure to the hormone; however, the enhancement of water flow was equal during each time interval before reaching the reaction maximum. A direct correlation between the value of ADH-stimulated water flow, cAMP content in bladder tissue and frequency of particle aggregates in the granular cell apical membrane was observed. The content of cAMP in ADH-treated bladders was higher by 80% in the absence than in the presence of an osmotic gradient. Pretreatment of urinary bladders with 50 microM cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, significantly accelerated the development of the hydroosmotic reaction and increased the magnitude of water flow in comparison with the effect of ADH only. No changes in cyclic AMP phosphodiesterase activity were found in the urinary bladder homogenates under the action of ADH, so it seems likely that accumulation of cAMP depends only on the increase of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates? 127 17

We studied cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes and their role in adenosine 3',5'-cyclic monophosphate (cAMP) and cGMP metabolism in a rat inner medullary collecting duct (IMCD) cell line. The homogenized and fractionated IMCD cells of cAMP-PDE and all of cGMP-PDE activity were found in the cytosol. The majority of cytosolic cAMP-PDE (greater than 50%) was isozyme PDE-IV; the Ca(2+)-calmodulin-sensitive PDE-I was present only in cytosol. Preincubation of IMCD cells with PDE-IV inhibitor rolipram markedly (5x) enhanced levels of cAMP both basal and in the presence of [Arg8]vasopressin (AVP). Cilostamide (for PDE-III) or vinpocetine had no effect, whereas PDE-I inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MeoM-IBMX) enhanced AVP-dependent cAMP levels. Exposure of IMCD cells to 2 microM ionomycin decreased both basal and AVP-stimulated cAMP. Depletion of Ca2+ by preincubation of IMCD cells in the Ca(2+)-free medium with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid markedly enhanced the stimulatory response of cAMP to AVP, and addition of 8-MeoM-IBMX further enhanced the AVP response. The levels of cGMP, basal or in response to atriopeptin (ANP), were not affected by PDE-V inhibitor zaprinast, but both inhibitors of PDE-I, 8-MeoM-IBMX and vinpocetine, increased basal cGMP, and 8-MeoM-IBMX also increased cGMP levels enhanced by ANP. The depletion of Ca2+ from IMCD cells alone had no effect on cGMP levels, but effects of 8-MeoM-IBMX and vinpocetine on the ANP-stimulated cGMP levels were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic 3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct cells. 132 Mar 33

To test the hypothesis that rapid adenosine 3',5'-cyclic monophosphate (cAMP) catabolism via cyclic 3',5'-nucleotide phosphodiesterase (PDE) is a cause of the unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI), we investigated properties of PDEs and other aspects of the VP-dependent cAMP-signaling system in segments of collecting ducts [inner medullary (IMCD), cortical (CCD), and outer medullary (OMCD) ducts] microdissected from control mice and mice with NDI. The activity of cAMP-PDE, but not of cGMP-PDE, was markedly higher in IMCD (+109%), and to a lesser degree in OMCD (+41%) and CCD (+27%), of NDI mice than in normal controls. The cAMP-PDE in IMCD of NDI mice was more sensitive to inhibition by the PDE isozyme-specific inhibitors rolipram and cilostamide, but not by 3-isobutyl-1-methylxanthine, than was the cAMP-PDE in controls. Levels of cAMP in intact IMCD and CCD from NDI mice completely failed to increase in response to 10(-6) M VP. Incubation with rolipram alone, but not with cilostamide alone, restored VP-dependent cAMP accumulation in IMCD of NDI mice to the levels found in control mice; addition of cilostamide further enhanced the effect of rolipram. Analogous (but quantitatively lesser) anomalies of the VP-dependent cAMP system, including the effects of PDE inhibitors, were observed also in CCD of NDI mice. However, the activity of VP-stimulated adenylate cyclase assayed in permeabilized IMCD did not differ in NDI and control mice. These results indicate that anomalously high activities of low-Km cAMP-PDE isozymes account for the failure of collecting ducts of NDI mice to increase cAMP levels in response in VP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of cAMP-phosphodiesterase isozymes in pathogenesis of murine nephrogenic diabetes insipidus. 165 9

In mice with hereditary nephrogenic diabetes insipidus (NDI), the inability of vasopressin to increase hydraulic water permeability is reflected in a lack of intramembranous particle (IMP) clusters in apical membranes of inner medullary collecting ducts. The lack arises from anomalously high activity of one or two isozymes of adenosine 3',5'-cyclic monophosphate-phosphodiesterase (cAMP-PDE). We asked whether inhibition of these isozymes with rolipram and cilostamide would raise not only the tissue content of cAMP but also and simultaneously restore IMP clusters. Inner medullary collecting ducts from NDI mice were incubated in vitro. Tissue content of cAMP (fmol of cAMP per bundle) and number of IMP clusters (per 100 microns 2 of principal cell apical membrane) were, respectively: control, 44.8 +/- 13.0 and 4.16 +/- 1.49; arginine vasopressin (AVP), 31.7 +/- 8.0 and 3.98 +/- 1.56; rolipram and cilostamide, 109.7 +/- 21.0 and 58.09 +/- 15.74; and AVP plus rolipram and cilostamide, 305.7 +/- 75 and 48.63 +/- 11.03 (with the last four values showing significant difference from control and AVP only, respectively). In addition, treating NDI mice with rolipram and cilostamide in vivo reduced their high fluid turnover. We conclude that failure by AVP to increase cAMP in cells of collecting ducts, which results from anomalously high activity of one or two specific isozymes of cAMP-PDE, is the major or sole cause for the excretion of hypotonic urine in NDI mice (DI +/+ Severe strain).
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PMID:Induction of intramembranous particle clusters in mice with nephrogenic diabetes insipidus. 165 82

In a strain of mice called DI +/+ Severe, nephrogenic (or vasopressin-resistant) diabetes insipidus is caused by an inability of the antidiuretic hormone (ADH, or vasopressin) to increase the water permeability of the renal collecting system. That inability, in turn, arises from abnormally high activity of the enzyme cAMP-phosphodiesterase, specifically of the isozyme type III (PDE-III), which hydrolyzes cAMP and prevents the intracellular buildup of this second messenger. Two rather specific inhibitors of PDE-III, rolipram and cilostamide, used either in vitro or in vivo, reverse the deficiencies in DI +/+ Severe mice by increasing intracellular cAMP and water permeability toward or to their normal values. These results have implications for the treatment of nephrogenic diabetes insipidus in human patients.
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PMID:Causes of the urinary concentrating defect in mice with nephrogenic diabetes insipidus. 216 65

Vasopressin has been shown previously to lower the glucagon-induced increase of cyclic AMP levels in isolated rat hepatocytes by way of an enhanced phosphodiesterase (EC 3.1.4.17) activity. Five phosphodiesterase inhibitors were tested for their ability to prevent vasopressin from lowering cyclic AMP levels in intact hepatocytes and for their inhibitory effect in vitro on soluble and particulate phosphodiesterase activities partially purified from hepatocytes. Three soluble activities have been separated by DEAE-cellulose chromatography: a phosphodiesterase hydrolyzing both cyclic AMP and cyclic GMP, a form stimulated by cyclic GMP and a cyclic AMP-specific activity. The absence of any statistically significant correlation between the in vivo (in intact cells) and the in vitro (on isolated phosphodiesterases) potencies of the inhibitors does not support a role for the cytosolic phosphodiesterases in mediating the vasopressin-induced decrease in cyclic AMP levels. No statistically significant correlation was observed between the inhibition of the vasopressin effect on cyclic AMP accumulation and the inhibition of phosphodiesterase activity either associated with the native plasma membranes or solubilized from these membranes with 0.4 M NaCl. In contrast, a statistically significant correlation was observed between the degree of inhibition of the vasopressin effect in the intact cells and the degree of inhibition of the intrinsic phosphodiesterase still associated with the plasma membranes after high-salt treatment. These data indicate that a phosphodiesterase activity integral to the plasma membrane is very likely involved in the negative control of cyclic AMP levels by vasopressin.
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PMID:Involvement of a plasma membrane phosphodiesterase in the negative control of cyclic AMP levels by vasopressin in rat hepatocytes. 284 89

Addition of the cAMP derivatives butcAMP or 8BrcAMP to quiescent cultures of Swiss 3T3 causes synergistic stimulation of DNAk synthesis with insulin, phorbol esters, vasopressin, epidermal growth factor, or fetal bovine serum (2-5%). In the presence of insulin, 8BrcAMP, and butcAMP stimulate [3H]-thymidine incorporation into acid-precipitable material in a dose-dependent manner. The effect of these agents is specific since 8Br5'AMP, 5'AMP, butyrate, or 8BrcGMP fail to stimulate DNA synthesis under identical experimental conditions. Furthermore, the mitogenic effects of the cAMP derivatives were markedly potentiated by 1-methyl-3-isobutyl xanthine and 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidine, both of which are potent inhibitors of cyclic nucleotide phosphodiesterase activity. The growth-promoting effects of the cAMP derivatives were demonstrated by [3H]-thymidine incorporation (either by scintillation counting or by autoradiography), by flow cytofluorometric analysis, and by increase in cell number. When quiescent Swiss 3T3 cells were exposed to butcAMP and insulin, DNA synthesis began after a lag of 17h. The result of sequential additions of cAMP derivatives and insulin to quiescent 3T3 cells suggest that these agents must act simultaneously in G0/G1 to stimulate entry into DNA synthesis in these cells. The findings support the proposition that an increase in cellular levels of cAMP (but not cGMP) act sas a mitogenic stimulus for confluent and quiescent Swiss 3T3 cells.
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PMID:Synergistic stimulation of DNA synthesis by cyclic AMP derivatives and growth factors in mouse 3T3 cells. 628 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

Kidney function is regulated by several hormones which act through adenylate cyclase-cyclic AMP system. The present study was undertaken to investigate cyclic AMP- and cyclic GMP-phosphodiesterase (cAMP-PDE and cGMP-PDE respectively) activities in the rat kidney, and also the effect of several hormones affecting the kidney function on these enzyme activities in vitro. Rat kidneys were separated into cortex and medulla. These were homogenized in 50 mM Tris-HCl buffer, pH 7.5, containing 0.32 M sucrose and fractionated by centrifugation. PDE activity was measured in all fractions, using the two-step assay system. A low substrate concentration (0.5 microM) was used, unless otherwise stated. Substantial activity was present in all of the fractions and most of the activity existed in the soluble fraction (105000 X g supernatant). Cyclic GMP-PDE activity was dominant in both cortex and medulla. The rat kidney contained two forms of cAMP-PDE, one of which had a Km of 2.0 X 10(-4) M and another which had a low Km of 2.5 X 10(-5) M, and one form of cGMP-PDE with a Km of 2.5 X 10(-5) M. These cAMP-PDE and cGMP-PDE were purified by Sepharose-6B column chromatography. Cyclic AMP-PDE activity was found in a broad area associated with two peaks and cGMP-PDE activity had one peak corresponding to the same peak as the high molecular weight cAMP-PDE. Calmodulin was eluted after the peak of cGMP-PDE activity. Both cAMP-PDE and cGMP-PDE activities were inhibited by calcium ion at a concentration of more than 5.0 X 10(-4) M. Cyclic GMP-PDE activity was not activated by calmodulin in the presence of enough calcium ion. The effect of 1 alpha, 25(OH)2 Vit D3, parathyroid hormone (PTH), antidiuretic hormone (ADH), calcitonin (CT), angiotensin II, and trichlormethiazide on the partially purified cAMP-PDE and cGMP-PDE activities were examined. 1 alpha, 25(OH)2 Vit D3 activated cAMP-PDE activity and did not affect cGMP-PDE activity. The concentrations of 1 alpha, 25(OH)2 Vit D3 producing 50% activation of cAMP-PDE activity were 5.0 X 10(-11) M (cortex) and 6.7 X 10(-10) M (medulla). CT and ADH inhibited both cAMP-PDE activities. The concentrations of CT producing 50% inhibition of cAMP-PDE activity were 4.0 X 10(-5) M (cortex) and 3.3 X 10(-7) M (medulla), and those of cGMP-PDE activity were 1.0 X 10(-5) M (cortex) and 1.0 X 10(-4) M (medulla). Concerning ADH, the concentrations required for 50% inhibition of cAMP-PDE activity were 5.3 X 10(-6) M (cortex) and about 1.0 X 10(-3) M (medulla), and those of cGMP-PDE activity were 5.3 X 10(-3) M (cortex) and 5.3 X 10(-8) M (medulla).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Effect of several hormones on cyclic 3',5'-nucleotide phosphodiesterase in rat kidneys]. 631 6


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