Cyclic 3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct cells

Yamaki, Masahiro; McIntyre, Steven J.; Rassier, Mark E.; Schwartz, Joel; Douša, Thomas P.

doi:10.1152/ajprenal.1992.262.6.f957

Cited by 19 publications

(24 citation statements)

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“…11B, there was a general correlation between the magnitudes of abundance change, as determined by immunoblotting and ICAT, which improved when proteins identified on the basis of only one peptide were excluded. Figure 12 shows a bioinformatic network representing the relationships between the core signaling pathway downstream from V2R occupation in IMCD demonstrated by previous studies (2,3,5,8,13,14,18,23,29,36) and the five proteins regulated in response to long-term dDAVP administration that were validated by immunoblotting in this study (see above). The connections between the newly identified proteins and the core network were generated through manual and computeraided literature searching (IPA and MetaCore; see METHODS).…”

Section: Quantitative Lc-ms/ms Analysis Of Response To Long-term Ddavmentioning

confidence: 58%

“…The proteins that significantly changed in abundance based on immunoblotting were cathepsin D, GAPDH, heat shock 70-kDa protein (Hsp70), Rap1, and syntaxin-7. The responses were analyzed further by carrying out network analysis incorporating the core signaling pathway downstream from V2R occupation in IMCD demonstrated by previous studies (2,3,5,8,13,14,18,23,29,36) and the five proteins validated by immunoblotting as described above. The functional interactions between proteins were culled from the literature through manual and computeraided searching (IPA and MetaCore).…”

Section: Discussionmentioning

confidence: 99%

“…This analysis used the core signaling pathway downstream from V2R occupation in IMCD demonstrated by previous studies (2,3,5,8,13,14,18,23,29,36) as the core network. The connections between the newly identified proteins and the core network were created through manual and computer-aided literature searching [Ingenuity Pathway Analysis (IPA), Ingenuity Systems, Mountain View, CA, http://www.ingenuity.com; and MetaCore, GeneGo, St. Joseph, MI, http://www.genego.com].…”

Section: Bioinformatic Network Analysismentioning

confidence: 99%

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High-throughput identification of IMCD proteins using LC-MS/MS

Pisitkun

Bieniek

Tchapyjnikov

et al. 2006

Physiological Genomics

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per. High-throughput identification of IMCD proteins using LC-MS/ MS. Physiol Genomics 25: 263-276, 2006. First published January 31, 2006 doi:10.1152/physiolgenomics.00214.2005.-The inner medullary collecting duct (IMCD) is an important site of vasopressinregulated water and urea transport. Here we have used protein mass spectrometry to investigate the proteome of the IMCD cell and how it is altered in response to long-term vasopressin administration in rats. IMCDs were isolated from inner medullas of rats, and IMCD proteins were identified by liquid chromatography/tandem mass spectrometry (LC-MS/MS). We present a WWW-based "IMCD Proteome Database" containing all IMCD proteins identified in this study (n ϭ 704) and prior MS-based identification studies (n ϭ 301). We used the isotope-coded affinity tag (ICAT) technique to identify IMCD proteins that change in abundance in response to vasopressin. Vasopressin analog (dDAVP) or vehicle was infused subcutaneously in Brattleboro rats for 3 days, and IMCDs were isolated for proteomic analysis. dDAVP and control samples were labeled with different cleavable ICAT reagents (mass difference 9 amu) and mixed. This was followed by one-dimensional SDS-PAGE separation, in-gel trypsin digestion, biotin-avidin affinity purification, and LC-MS/MS identification and quantification. Responses to vasopressin for a total of 165 proteins were quantified. Quantification, based on semiquantitative immunoblotting of 16 proteins for which antibodies were available, showed a high degree of correlation with ICAT results. In addition to aquaporin-2 and ␥-epithelial Na channel (␥-ENaC), five of the immunoblotted proteins were substantially altered in abundance in response to dDAVP, viz., syntaxin-7, Rap1, GAPDH, heat shock protein (HSP)70, and cathepsin D. A 28-protein vasopressin signaling network was constructed using literature-based network analysis software focusing on the newly identified proteins, providing several new hypotheses for future studies.inner medullary collecting duct; systems biology; mass spectrometry; liquid chromatography; aquaporin-2; epithelial Na channel; vasopressin VASOPRESSIN CONTROLS RENAL WATER excretion in part by regulating the permeability of collecting duct cells to water. The main protein target for this process is the water channel aquaporin-2 (AQP2). Vasopressin regulates AQP2 in two ways to increase collecting duct water permeability (28). 1) Over a period of minutes, vasopressin stimulates trafficking of AQP2-containing vesicles to the apical region of the collecting duct cells where they fuse with the plasma membrane to increase water permeability. 2) Over a period of hours to days, vasopressin increases AQP2 protein abundance in the collecting duct cells, in part due to increased transcription of the AQP2 gene. The signaling pathways involved in these responses remain incompletely understood.In recent years, large-scale identification of proteins by mass spectrometry has become practical, and such techniques are finding increasing use in the discov...

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Section: Quantitative Lc-ms/ms Analysis Of Response To Long-term Ddavmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Bioinformatic Network Analysismentioning

confidence: 99%

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High-throughput identification of IMCD proteins using LC-MS/MS

Pisitkun

Bieniek

Tchapyjnikov

et al. 2006

Physiological Genomics

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“…Given the multiplicity of its actions in cells, calmodulin likely plays other physiologically significant roles in the IMCD. One such role is stimulation of phosphodiesterase activity, which has been demonstrated in prior studies (49,50). The potential attenuation of the cAMP response via CaM-sensitive phosphodiesterase-1 has not been addressed in this study.…”

Section: Discussionmentioning

confidence: 88%

Calmodulin Is Required for Vasopressin-stimulated Increase in Cyclic AMP Production in Inner Medullary Collecting Duct

Hoffert

Chou

Fenton

et al. 2005

Journal of Biological Chemistry

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Calmodulin plays a critical role in regulation of renal collecting duct water permeability by vasopressin. However, specific targets for calmodulin action have not been thoroughly addressed. In the present study, we investigated whether Ca 2؉ /calmodulin regulates adenylyl cyclase activity in the renal inner medullary collecting duct. Rat inner medullary collecting duct suspensions were incubated in the presence or absence of 0.1 nM vasopressin and the calmodulin inhibitors, monodansylcadaverine, W-7, and trifluoperazine, followed by measurement of cAMP. Vasopressin-stimulated cAMP elevation was significantly attenuated in the presence of calmodulin inhibitors. Analysis of transglutaminase 2 knock-out mice confirmed that these compounds were not acting through inhibition of transglutaminase 2 activity. Calmodulin inhibitors also blocked both cholera toxin-and forskolinstimulated cAMP accumulation. In isolated perfused tubules, W-7 reversibly blocked vasopressin-stimulated urea permeability, a process that requires a rise in intracellular cAMP but does not appear to involve protein trafficking to the apical plasma membrane. These results suggest that calmodulin is required for vasopressinstimulated adenylyl cyclase activity in the intact inner medullary collecting duct. Reverse transcription-PCR, immunoblotting, and immunohistochemistry revealed the presence of the calmodulin-sensitive adenylyl cyclase type 3 in the rat collecting duct, an isoform previously not known to be expressed in the collecting duct. Long-term treatment of Brattleboro rats with a vasopressin analog markedly decreased adenylyl cyclase type 3 protein abundance, providing an explanation for long-term down-regulation of vasopressin response in the collecting duct. These studies demonstrate the importance of calmodulin in the regulation of collecting duct adenylyl cyclase activity and transport function.

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“…24,25,39 In rat IMCD cells, PDE1 inhibition enhanced AVP-dependent cAMP levels and increased cGMP, indicating that PDE1 plays a dual role by regulating cAMP and cGMP in these cells. 40 By contrast, PDE4 was found to be the predominant isoform for cAMP metabolism in extracts from suspensions of renal cortical tubules. 39 Because PDE1 is regulated by Ca 2+ and concentrations of Ca 2+ vary widely within the cell, PDE1 may be the major PDE involved in hydrolyzing cAMP within cellular domains with high Ca 2+ , and the relative contribution of PDE1 to total PDE activity may depend on cellular conditions.…”

Section: Discussionmentioning

confidence: 93%

Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney Disease

Pinto¹,

Raman²,

Reif³

et al. 2016

Journal of the American Society of Nephrology

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cAMP stimulates cell proliferation and Cl--dependent fluid secretion, promoting the progressive enlargement of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). Intracellular cAMP levels are determined by the balance of cAMP synthesis by adenylyl cyclases and degradation by phosphodiesterases (PDEs). Therefore, PDE isoform expression and activity strongly influence global and compartmentalized cAMP levels. We report here that PDE3 and PDE4 expression levels are lower in human ADPKD tissue and cells compared with those of normal human kidneys (NHKs), whereas PDE1 levels are not significantly different. Inhibition of PDE4 caused a greater increase in basal and vasopressin (AVP)-stimulated cAMP levels and Cl -secretion by ADPKD cells than inhibition of PDE1, and inhibition of PDE4 induced cyst-like dilations in cultured mouse Pkd1 2/2 embryonic kidneys. In contrast, inhibition of PDE1 caused greater stimulation of extracellular signal-regulated kinase (ERK) and proliferation of ADPKD cells than inhibition of PDE4, and inhibition of PDE1 enhanced AVP-induced ERK activation. Notably, inhibition of PDE1, the only family of Ca 2+-regulated PDEs, also induced a mitogenic response to AVP in NHK cells, similar to the effect of restricting intracellular Ca 2+. PDE1 coimmunoprecipitated with B-Raf and A-kinase anchoring protein 79, and AVP increased this interaction in ADPKD but not NHK cells. These data suggest that whereas PDE4 is the major PDE isoform involved in the regulation of global intracellular cAMP and Cl -secretion, PDE1 specifically affects the cAMP signal to the B-Raf/MEK/ERK pathway and regulates AVP-induced proliferation of ADPKD cells.

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Cyclic 3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct cells

Cited by 19 publications

References 0 publications

High-throughput identification of IMCD proteins using LC-MS/MS

High-throughput identification of IMCD proteins using LC-MS/MS

Calmodulin Is Required for Vasopressin-stimulated Increase in Cyclic AMP Production in Inner Medullary Collecting Duct

Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney Disease

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