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)

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

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

ANP stimulates a profound natriuresis and diuresis by a series of concerted actions along the nephron, including stimulation of glomerular filtration and inhibition of net salt and water reabsorption in the cortical and inner medullary collecting ducts. Several actions of ANP contribute to its natriuretic and diuretic effects in the collecting duct. These include reductions in aldosterone secretion, increases in hydrostatic pressures opposing Na+ reabsorption, possible stimulation of medullary washout, and direct inhibition of salt and water transport. In both CCD and IMCD, ANP antagonizes the hydroosmotic actions of vasopressin, which leads to diuresis. The mechanisms by which ANP inhibits response to vasopressin remain unclear, although in IMCD, cGMP can duplicate the response to ANP. In CCD, ANP can inhibit Na+ reabsorption via cGMP; the transport pathway regulated by ANP is unknown. In IMCD, ANP acting via cGMP inhibits a conductive Na+ or cation channel, which appears to be on the luminal membrane.
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PMID:Renal actions of atrial natriuretic peptide: regulation of collecting duct sodium and water transport. 213 59

Whereas interactions between antidiuretic hormone (ADH) and prostaglandins (PGs) have been reported in the cortical collecting tubule (CCD), the precise effects of arginine vasopressin (AVP) and its analogue, 1-desamino-8-D-arginine vasopressin (dDAVP) on PGE2 synthesis remain controversial. We examined the dynamic response of PGE2 synthesis to these two analogues in isolated rabbit CCD. Microdissected CCD were superfused, and basal and hormone-induced PGE2 synthesis were determined by enzyme immunoassay. Addition of arachidonic acid (AA) steeply increased basal PGE2 synthesis, in the 0-1 microM-dose range. The presence of AA was necessary to obtain a stimulatory effect of AVP on PGE2 synthesis. AVP induced an immediate, transitory, and dose-dependent stimulation of PGE2 synthesis. A maximal effect was obtained at 10(-8) M; PGE2 synthesis was increased by approximately 150-200% over the basal synthesis. With dDAVP, a very weak response was obtained only at 10(-7) M. From these results, we conclude that PGE2 synthesis in CCD is stimulated by ADH. This effect of ADH does not depend on the V2-receptor pathway and suggests the presence of V1-receptors in CCD.
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PMID:Effects of AVP and dDAVP on PGE2 synthesis in superfused cortical collecting tubules. 250 29

We have documented new observations with respect to PGE2 action in the rabbit CCD. (1) PGE2 can inhibit both cAMP and vasopressin-induced water flow, depending on the sequence of PGE2 addition with respect to vasopressin or cAMP. (2) PGE2 inhibition of vasopressin or cAMP-stimulated water flow can be reversed with staurosporine. Thus, PGE2 inhibits vasopressin-stimulated water flow by activation of PKC and (3) PGE2 induces release of calcium from intracellular stores. These results strongly suggest the presence of a PGE2 receptor coupled to PIP2 hydrolysis. PGE2 mediated increases in cytosolic calcium are responsible for the inhibitory action of PGE2 on sodium transport. While stimulation of cAMP production by PGE2 may contribute to the inhibition of sodium transport, it is not required since in the presence of 8-CPTcAMP, PGE2 still decreases sodium transport. The effect of PGE2 on sodium transport is pertussis toxin insensitive and is unlikely to be mediated by an inhibitory G protein. Using PGE2 and one of its selective analogues, sulprostone, we have provided evidence for functionally distinct PGE2 receptors. Separate PGE2 receptor subtypes appear to be coupled to separate transport processes. These receptor subtypes may correspond to the EP1, EP2 and EP3 receptors described earlier in smooth muscle. Thus, an EP2 like receptor stimulates cAMP generation and water reabsorption while an EP1 like receptor increases [Ca++]i and inhibits sodium reabsorption. Finally, an EP3 receptor, equivalently activated by sulprostone and PGE2, may couple to Gi and mediate pertussis toxin sensitive inhibition of vasopressin-stimulated water flow.
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PMID:Cellular signalling of PGE2 and its selective receptor analogue sulprostone in rabbit cortical collecting duct. 782 28

Because previous studies indicated that, in the rat collecting tubule, vasopressin (AVP)-sensitive adenylate cyclase (AC) is controlled by mineralocorticoids in the long term, the present study was designed to investigate whether such a control also exists in the short term. Therefore, we investigated the in vivo and in vitro effects of aldosterone on AC activity in cortical and outer medullary collecting tubules (CCD and OMCD, respectively) from adrenalectomized rats. Injection of aldosterone (10 micrograms/kg body wt) to adrenalectomized rats restored within 3 h AVP-sensitive AC activity in the CCD and OMCD up to the levels observed in the corresponding segments of adrenal intact rats. Similarly, incubating CCD or OMCD from adrenalectomized rats for 2.5 h in the presence of 10(-8) M aldosterone enhanced AVP-sensitive AC activity up to values similar to those found in normal rats. In vitro stimulation of AVP-sensitive AC activity was dose dependent with regard to aldosterone [apparent affinity constant (K0.5) approximately 10(-9) M], appeared after a 30-min lag period, and reached its maximum after 2-2.5 h. In addition, it was totally abolished by the antimineralocorticoid spironolactone, whereas the specific glucocorticoid antagonist RU 38486 had no effect. Finally, actinomycin D and cycloheximide totally abolished the in vitro action of aldosterone, demonstrating the involvement of protein synthesis in that process.
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PMID:Short-term effect of aldosterone on vasopressin-sensitive adenylate cyclase in rat collecting tubule. 849 34

The apical small-conductance K+ channel plays an important role in renal K+ secretion, as evidenced by the presence of the extensive modulatory pathways. Figure 3 summarizes the current understanding of the mechanisms that modulate the apical small-conductance K+ channel. Stimulation of adenylate cyclase enhances channel activity and consequently K+ secretion. In contrast, increases in intracellular Ca2+ concentration and activation of Ca(2+)-dependent signal transduction pathways inhibit the K+ channel and thus decrease K+ secretion. The vasopressin-induced stimulation of K+ secretion in CCD results at least in part from cAMP-dependent signal transduction pathways. The Ca(2+)-dependent signal transduction pathway is responsible for modulatory coupling between Na+ pump turnover and apical K+ conductance when the Na+ pump is inhibited.
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PMID:View of K+ secretion through the apical K channel of cortical collecting duct. 856 63

Recently we clarified the mechanism in which arginine-vasopressin (AVP) applied from the luminal side inhibits the basolateral Cl- conductance, which is stimulated by basolateral AVP. However, to prove that these vasopressin phenomena are expressed via receptor mediated actions, we examined the effect of specific V1 and V2 receptor antagonists, OPC-21268 and OPC-31260, respectively, on the electrical response to vasopressin in the rabbit CCD perfused in vitro. In the presence of the V2-antagonist, basolateral AVP caused only the activation of luminal Na+ conductance, indicating a V1 action. In the presence of the V1 antagonist, basolateral AVP caused the same biphasic responses in electrical parameters as cyclic AMP, representing a pure V2 action. On the other hand, a rise in cell Ca2+ in response to AVP was completely abolished in the presence of the V1-antagonist, but not by the V2-antagonist in the bath. These data confirm our earlier findings that rabbit CCD possesses both V1 and V2 receptors in the basolateral membrane. We conclude that electrical responses to AVP in the rabbit CCD are a complex of V1 and V2 receptor-mediated actions.
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PMID:Functional characterization of vasopressin V1 and V2 receptors in the rabbit renal cortical collecting duct. 874 49

The purpose of the present study was to examine whether there is axial heterogeneity in the basolateral plasma membrane (BLM) localization of AQP2 and whether altered vasopressin action or medullary tonicity affects the BLM localization of AQP2. Immunocytochemistry and immunoelectron microscopy revealed AQP2 labeling of the BLM in connecting tubule (CNT) cells and inner medullary collecting duct (IMCD) principal cells in normal rats and vasopressin-deficient Brattleboro rats. In contrast there was little basolateral AQP2 labeling in cortical (CCD) and outer medullary collecting duct principal cells. Short-term desamino-Cys(1), (D)-Arg(8) vasopressin (dDAVP) treatment (2 h) of Brattleboro rats caused no increase in AQP2 labeling of the BLM. In contrast, long-term dDAVP treatment (6 days) of Brattleboro rats caused an increased BLM labeling in CNT, CCD, and IMCD. Treatment of normal rats with V(2)-receptor antagonist for 60 min caused retrieval of AQP2 from the apical plasma membrane. Moreover, AQP2 labeling of the BLM was unchanged in CNT and IMCD but increased in CCD. In conclusion, there is an axial heterogeneity in the subcellular localization of AQP2 with prominent AQP2 labeling of the BLM in CNT and IMCD. There was no increase in AQP2 labeling of the BLM in response to short-term dDAVP. Moreover, acute V(2)-receptor antagonist treatment did not cause retrieval of AQP2 from the BLM. In contrast, long-term dDAVP treatment caused a major increase in AQP2 expression in the BLM in CCD.
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PMID:Axial heterogeneity in basolateral AQP2 localization in rat kidney: effect of vasopressin. 1245 71

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