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 effect of vasopressin analogues on plasma adenosine 3',5'-cyclic monophosphate (cAMP) concentration was examined in a group of five conscious dogs instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter). These dogs were infused for 20 min with a selective antidiuretic (V2) agonist, desamino-8-D-arginine vasopressin (DDAVP, 10 ng.kg-1 x min-1). This infusion was repeated on another day in the presence of the combined V1-V2 antagonist d(CH2)5-D-Tyr(Et)-4-valine,8-arginine vasopressin. The dogs also received an infusion of the selective V1 agonist 2-phenylalanine,8-ornithine oxytocin (Phe-OrnOT) at a rate of 10 ng.kg-1 x min-1. The effect of these infusions was compared with those of an isotonic saline infusion. Plasma cAMP measured in the aorta remained unchanged during all infusions but that of the selective V2 agonist DDAVP alone, during which it increased significantly from 22.4 +/- 0.8 to 32.6 +/- 4.6 and 37.0 +/- 4.1 pmol/ml after 10 and 20 min, respectively. In the plasma sampled from the inferior vena cava caudal to the renal veins, cAMP increased during DDAVP infusion from 22.2 +/- 2.5 to 39.2 +/- 3.8 and 36.0 +/- 4.0 pmol/ml after 10 and 20 min, respectively. The infusion of DDAVP was later given to the same dogs under anesthesia after bilateral nephrectomy, which did not modify the effect of DDAVP on arterial plasma cAMP. In another group of four conscious dogs, infusion of DDAVP at the same rate did not induce significant changes in plasma catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:cAMP and extrarenal vasopressin V2 receptors in dogs. 133 16

1. The effect of the microtubule-disruptive agent, colcemid (N-deacetyl-N-methyl-colchicine), on the water permeability response to vasopressin has been investigated in isolated cortical collecting tubules from the rabbit kidney perfused in vitro. 2. Pretreatment of collecting tubules with colcemid inhibited the increase in water permeability elicited by vasopressin, 50 microU ml-1, in a time- and dose-dependent manner. After 75 min exposure to the drug, inhibition of the response to the hormone averaged 72 +/- 6% (n = 4, P < 0.01) at a colcemid concentration of 7.2 x 10(-5) M. Inhibition was estimated to be half-maximal at a colcemid concentration of 1.9 x 10(-6) M. 3. Colcemid, 2.7 x 10(-7) to 7.2 x 10(-5) M, had no effect on basal water permeability nor on the increase in lumen negative potential difference (PD) induced by the hormone. 4. Lumicolcemid, an isomer of colcemid that does not disrupt microtubules, had no influence on the water permeability response to vasopressin. 5. Pretreatment with colcemid, 2.7 x 10(-5) M, for 45 min inhibited the water permeability response to 8-CPT-cAMP, 1.8 x 10(-5) M, by 38 +/- 4% (n = 5, P < 0.01). 6. When collecting tubules were exposed to colcemid, 5.5 x 10(-5) M, for 45 min after the hydrosmotic response to vasopressin had been established, the drug had no influence on the maintenance of the raised water permeability. 7. The results provide further evidence that cytoplasmic microtubules play a role in the initiation of the hydrosmotic response to vasopressin in the mammalian collecting tubule at a site distal to the generation of cyclic AMP.
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PMID:Effect of colcemid on the water permeability response to vasopressin in isolated perfused rabbit collecting tubules. 133 5

Cyclic adenosine 3',5'-monophosphate (cAMP) has been implicated as an intracellular messenger mediating osmotic regulation of expression of the gene encoding the neuropeptide vasopressin (VP) in the hypothalamus. We have used a heterologous transient transfection system to demonstrate that cAMP regulates the bovine VP gene promoter following transfection into CV1 cells. Mutational analysis identified a bovine VP cAMP-responsive element (BVP-CRE) 120-112 base-pairs upstream of the start of transcription. DNase I footprint analysis using nuclear protein extract from CV1 cells showed protection at the site of the BVP-CRE. Protection of the BVP-CRE was also observed using purified AP1 protein, while there was a weak interaction with the BVP-CRE using purified rat CREB protein. Nuclear proteins purified from the rat supraoptic nucleus bind to the BVP-CRE. As transgenic mouse studies have shown that the bovine VP gene is subject to appropriate physiological regulation in the mouse hypothalamus (Ang, H. L., Funkhouser, J., Carter, D. A., Ho, M. Y., and Murphy, D. (1991) Soc. Neurosci. Abstr. 513, 12), these data indicate a role for the BVP-CRE element in mediating VP gene expression in vivo. These data demonstrate that cAMP regulates bovine VP gene expression in vitro via a cis-acting element within the VP promoter, and this activation may be mediated by members of the AP1/ATF/CREB family of transcription factors.
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PMID:The identification of a cis-acting element involved in cyclic 3',5'-adenosine monophosphate regulation of bovine vasopressin gene expression. 133 38

Metabolism of cAMP and cGMP by the major types (families) of cyclic-3',5'-nucleotide phosphodiesterases (PDE) was studied in confluent renal epithelial LLC-PK1 cells grown in vitro. LLC-PK1 cells mainly contain the cAMP-specific rolipram-sensitive PDE type-IV (PDE-IV), the Ca(2+)-calmodulin dependent PDE type-I and cGMP-specific PDE type-V; all these PDEs are mainly localized in cytosol. Analysis of PDE activities in soluble extract of LLC-PK1 cell homogenate by FPLC ionex chromatography on Mono-Q column also disclosed the presence of low activities of cGMP-stimulated PDE-II and PDE-III. Moreover, activity of PDE-IV was resolved into four distinct chromatographic peaks. The increase of cAMP level in response to incubation of intact LLC-PK1 cells with vasopressin (AVP) was markedly enhanced in the presence of rolipram, but not in the presence of other PDE isozyme-specific inhibitors. Incubation with AVP and atriopeptin (ANP) together resulted in increase in cGMP and a small decrease of cAMP accumulation in LLC-PK1 cells. Results of these studies first show that the LLC-PK1 cells contain all five major types of PDE isozymes where PDE-IV, PDE-I and PDE-V are quantitatively predominant. The rolipram-sensitive PDE-IV, present in several chromatographically distinct forms, appears to be the key PDE isozyme involved in control of cAMP generated in response to stimulation by AVP in LLC-PK1 cells.
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PMID:Isozymes of cyclic-3',5'-nucleotide phosphodiesterases in renal epithelial LLC-PK1 cells. 134 59

The ability of alpha 2-adrenoceptor agonists to inhibit vasopressin (VP)-stimulated cAMP accumulation in collecting tubules and to inhibit the antidiuretic effect of VP in rats is clearly established. However, in other species, such as the dog, alpha 2-adrenoceptor-induced inhibition of VP action has not been convincingly demonstrated. In the present study, we examined the effects of epinephrine and other alpha 2-adrenoceptor agonists on VP-stimulated cAMP accumulation in inner medullary collecting tubule cells and/or cortical collecting tubules from a number of species. Epinephrine, oxymetazoline, clonidine, and guanabenz inhibited VP-induced cAMP formation in rat inner medullary collecting tubule cells with IC50s ranging from 10 to 30 nM. However, epinephrine or guanabenz had no effect on VP-stimulated cAMP formation in cells from dog, pig, rhesus monkey, or human inner medulla. Similarly, epinephrine inhibited VP-induced cAMP accumulation in cortical collecting tubules dissected from rat kidneys but not from dog or rabbit kidneys. We conclude that there is a marked species difference in the ability of alpha 2-adrenoceptor agonists to inhibit VP-induced cAMP formation at the tubular level. This may explain the difficulty in demonstrating an alpha 2-adrenoceptor agonist-induced inhibition of VP action in other species such as dog and man.
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PMID:Inhibition of vasopressin-sensitive cAMP accumulation by alpha 2-adrenoceptor agonists in collecting tubules is species dependent. 134 26

We have reported that dopamine (DA) inhibits Na-K-ATPase activity in the cortical collecting duct (CCD) by stimulating the DA1 receptor, and the present study was designed to evaluate the mechanism of this effect. Short-term exposure (15-30 min) of microdissected rat CCD to DA, a DA1 agonist (fenoldopam), vasopressin (AVP), forskolin, or dibutyryl cAMP (dBcAMP), which increase cAMP content by different mechanisms, strongly (approximately 60%) inhibited Na-K-ATPase activity. 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, completely blocked Na-K-ATPase inhibition by DA or fenoldopam, and IP20, an inhibitor peptide of cAMP-dependent protein kinase A (PKA), abolished the Na:K pump effect of all the cAMP agonists listed above. To verify whether the mechanism of pump inhibition by agents that increase cell cAMP involves phospholipase A2 (PLA2), we used mepacrine, a PLA2 inhibitor, which also abolished Na-K-ATPase inhibition by DA or fenoldopam, as well as by AVP, forskolin, or dBcAMP. Arachidonic acid (10(-7) - 10(-4) M) inhibited Na-K-ATPase activity in dose-dependent fashion. Corticosterone, which induces lipomodulin, a PLA2 inhibitor protein inactivated by PKA, equally abolished the pump effects of DA, fenoldopam, forskolin, and dBcAMP, suggesting that lipomodulin might act between PKA and PLA2 in cAMP-dependent pump regulation. We conclude that dopamine inhibits Na-K-ATPase activity in the CCD through a DA1 receptor-mediated cAMP-PKA pathway that involves the stimulation of PLA2 and arachidonic acid release, possibly mediated by inactivation of lipomodulin. This pathway is shared by other agonists that increase cell cAMP and thus stimulate PKA activity.
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PMID:Intracellular signaling in the regulation of renal Na-K-ATPase. I. Role of cyclic AMP and phospholipase A2. 134 27

Because of the prominent role of the renal medulla in the elaboration of concentrated urine and the possible differential regulation of the various nephron segments, desensitization to vasopressin (AVP) was studied on freshly isolated rat medullary thick ascending limbs (MTALs) and outer medullary collecting ducts (MCDs). Desensitization was induced through intramuscular injections of 1-deamino-8-D-arginine-vasopressin (dDAVP, 2 micrograms/day for 3 days), the last of which was performed 1 h before kidney removal. The cellular response to AVP was studied by measuring cAMP accumulation in micro-dissected nephron segments. In the MTAL, we observed a marked (around 80%) and selective desensitization to AVP, the response to either glucagon or human calcitonin remaining unaltered. In the MCD, significant desensitization was observed in the presence of 1 nM AVP in the assay medium, and was no longer significant when the AVP concentration was increased to supramaximal levels (10-1,000 nM). These experiments thus reveal a clear dissociation between MTAL and MCD with regards to dDAVP-induced desensitization and extend previous observations made on target segments in the renal cortex.
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PMID:Desensitization to vasopressin action in the rat kidney medulla: studies on isolated nephron segments. 137 64

Three main pathways have been implicated in desensitization of receptors that stimulate adenylylcyclase (AC): cAMP-mediated phosphorylation; cAMP-independent phosphorylation, and receptor internalization. Cell lines derived from the murine Ltk- cell were found useful in exploring the contribution of cAMP-dependent phosphorylation in V2 vasopressin receptor desensitization. The HTB-2 cell expresses the human V2 vasopressin receptor, introduced by transfection of human genomic DNA, and the prostaglandin E1 (PGE1) receptor, endogenous to the Ltk- cell. The A7 cell expresses the hamster beta 2-adrenoceptor, which undergoes the above-mentioned desensitization processes. Treatment of HTB-2 cells with arginine-vasopressin (AVP) had no effect on AC responsiveness to PGE1, but promoted desensitization of the AVP response. This was seen as a 5-6-fold right shift in the dose-response curves for AVP action (cAMP accumulation in intact cells and AC stimulation in homogenates and isolated membranes) and in a decrease in the maximum effect of AVP on these parameters. AVP treatment caused a decrease in cell surface receptors to approximately 75% of control without changes in KD, as determined by Scatchard analysis. When cAMP was increased by treatment with 10 microM PGE1 and isobutylmethylxanthine, desensitization of the PGE1 receptor was observed but not of the AVP receptor. In A7 cells the same treatment caused, as expected, a 3-fold right shift in the dose-response curve for AC stimulation by isoproterenol, indicating that L cells can mediate heterologous desensitization. These data demonstrate that the V2 vasopressin and the PGE1 receptors undergo homologous desensitization in the absence of cAMP-mediated phosphorylation and that this component is not required for vasopressin receptor internalization.
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PMID:Desensitization of the human V2 vasopressin receptor. Homologous effects in the absence of heterologous desensitization. 137 12

Acidification of the endosomal pathway is important for ligand and receptor sorting, toxin activation, and protein degradation by lysosomal acid hydrolases. Fluorescent probes and imaging methods were developed to measure pH to better than 0.2 U accuracy in individual endocytic vesicles in Swiss 3T3 fibroblasts. Endosomes were pulse labeled with transferrin (Tf), alpha 2-macroglobulin (alpha 2M), or dextran, each conjugated with tetramethylrhodamine and carboxyfluorescein (for pH 5-8) or dichlorocarboxyfluorescein (for pH 4-6); pH in individual labeled vesicles was measured by ratio imaging using a cooled CCD camera and novel image analysis software. Tf-labeled endosomes acidified to pH 6.2 +/- 0.1 with a t1/2 of 4 min at 37 degrees C, and remained small and near the cell periphery. Dextran- and alpha 2M-labeled endosomes acidified to pH 4.7 +/- 0.2, becoming larger and moving toward the nucleus over 30 min; approximately 15% of alpha 2M-labeled endosomes were strongly acidic (pH less than 5.5) at only 1 min after labeling. Replacement of external Cl by NO3 or isethionate strongly and reversibly inhibited acidification. Addition of ouabain (1 mM) at the time of labeling strongly enhanced acidification in the first 5 min; Tf-labeled endosomes acidified to pH 5.3 without a change in morphology. Activation of phospholipase C by vasopressin (50 nM) enhanced acidification of early endosomes; activation of protein kinase C by PMA (100 nM) enhanced acidification strongly, whereas elevation of intracellular Ca by A23187 (1 microM) had no effect on acidification. Activation of protein kinase A by CPT-cAMP (0.5 mM) or forskolin (50 microM) inhibited acidification. Lysosomal pH was not affected by ouabain or the protein kinase activators. These results establish a methodology for quantitative measurement of pH in individual endocytic vesicles, and demonstrate that acidification of endosomes labeled with Tf and alpha 2M (receptor-mediated endocytosis) and dextran (fluid-phase endocytosis) is sensitive to intracellular anion composition, Na/K pump inhibition, and multiple intracellular second messengers.
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PMID:Second messengers regulate endosomal acidification in Swiss 3T3 fibroblasts. 138 79

There is convincing evidence to suggest that there are direct effects of adrenergic agents on renal tubules. During the last several years, considerable progress has been made in determining the type of adrenoceptors present in renal tubular cells through the use of radioligand binding and signal transduction methods. The receptor data are summarized in table 6. Almost all major nephron segments seem to have alpha 1- and alpha 2-adrenoceptors. However, there are few data describing the subtypes of alpha 1- or alpha 2-adrenoceptors in these segments. beta-Adrenoceptors are present in the CNT and collecting ducts of almost all species and in the thick ascending limbs of rats and mice. Adrenergic mediated signal transduction has been examined in some nephron segments, but virtually nothing is known about the relationship between the generation of adrenoceptor-mediated second messengers and changes in phosphorylation/activity of transport proteins (ion channels, ion pumps) in different types of renal tubular cells. There is general agreement that gluconeogenesis in the PCT is mediated by alpha 1-adrenoceptors through the PI and Ca2+ messenger system. Evidence also indicates that the increase in Na+ transport associated with renal nerve stimulation or adrenergic agonists in the PCT or the loop of Henle is mediated by alpha 1-adrenoceptors. Adrenergic agents modulate the effect of other hormones, such as PTH and vasopressin, on renal tubule transport by a decrease in cAMP, and this effect is mediated by alpha 2-adrenoceptors. There may be some interaction between the two alpha subtype-mediated effects in some nephron segments. beta-Adrenergic agonists stimulate cAMP formation in the PST, thick ascending limb (rat and mouse), CNT, and collecting duct segments. The physiological role of the beta-adrenoceptors in the PST is not known. beta-Adrenergic agonists stimulate sodium reabsorption by activation of the basolateral Cl- channel in the thick ascending limbs of rat and mice. The activation of beta-adrenoceptors in the CNT and CCD increases Cl- reabsorption and HCO3- secretion by stimulation of Cl/HCO3 exchange in the apical membrane of type B intercalated cell. The antikaliuretic effect of beta-adrenergic agonists is probably due to the stimulation of K+ reabsorption in type A intercalated cells in the CCD and OMCD. In the case of cholinergic drugs, the data in the literature are consistent with a model in which cholinergic agents increase papillary blood flow, resulting in the washout of the hypertonic medullary interstitium. This leads to a decrease in water abstraction out of the descending limb of Henle's loop.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Actions of adrenergic and cholinergic drugs on renal tubular cells. 155 26

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