Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure

Bertuccio,; Ibarra,; Pignataro,; Toledo,; Paz,; Arrizurieta,; [], Martin

doi:10.1046/j.1365-201x.1998.00411.x

Cited by 3 publications

(3 citation statements)

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“…In other pathological conditions, it has been described that DA does not modify Na + K + ATPase activity because some steps in the signaling cascade are disrupted. [37,38] In addition, previous results [39] have demonstrated that basal levels of intracellular cAMP in the microdissected mTAL are increased in this CRF model. Thus, vasopressin and calcitonin stimulated mTAL adenylate-cyclase in a dose-dependent manner in control rats but failed to stimulate it in CRF.…”

Section: Discussionmentioning

confidence: 92%

Mechanisms of PKC-Dependent Na⁺K⁺ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

et al. 2007

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The present work was designed to study Na + K + ATPase α1-subunit phosphorylation in rats with chronic renal failure (CRF) in comparison with normal rats. Na + K + ATPase α1-subunit phosphorylation degree was measured by binding the McK-1 antibody to dephosphorylated Ser-23 in microdissected medullary thick ascending limb of Henle (mTAL) segments. In addition, the total Na + K + ATPase α1-subunit expression and activity were also measured in the outer renal medulla homogenates and membranes.CRF rats showed a higher Na + K + ATPase activity, as compared with control rats (18.95 ± 2.4 vs. 11.21 ± 1.5 μmol Pi/mg prot/h, p < 0.05), accompanied by a higher total Na + K + ATPase expression (0.54 ± 0.04 vs. 0.27 ± 0.02 normalized arbitrary units (NU), p < 0.05). When McK-1 antibody was used, a higher immunosignal in mTAL of CRF rats was observed, as compared with controls (6.3 ± 0.35 vs.4.1 ± 0.33 NU, p < 0.05). The ratio Na + K + ATPase α1-subunit phosphorylation / total Na + K + ATPase α1-subunit expression per μg protein showed a nonsignificant difference between CRF and control rats in microdissected mTAL segments (2.11 ± 0.12 vs.2.26 ± 0.18 NU, p = NS). The PKC inhibitor RO-318220 10 −6 M increased immunosignal (lower phosphorylation degree) in mTAL of CRF rats to 128.43 ± 7.08% (p < 0.05) but did not alter McK1 binding in control rats. Both phorbol 12-myristate 13-acetate (PMA) 10 −6 M and dopamine 10 −6 M decreased immunosignal in CRF rats, corresponding to a higher Na + K + ATPase α1-subunit phosphorylation degree at Ser-23 (55.26 ± 11.17% and 53.27 ± 7.12% compared with basal, p < 0.05). In mTAL of CRF rats, the calcineurin inhibitor FK-506 10 −6 M did not modify phosphorylation degree at Ser-23 of Na + K + ATPase α1-subunit (100.21 ± 3.00% compared with basal CRF). In control rats, FK 506 10M decreased the immunosignal, which corresponds to a higher Na + K + ATPase α1-subunit phosphorylation degree at Ser-23. The data suggest that the regulation of basal Na + K + ATPase α1-subunit phosphorylation degree at Ser-23 in mTAL segments of CRF rats was primarily dependent on PKC activation rather than calcineurin dependent mechanisms.

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Section: Discussionmentioning

confidence: 92%

Mechanisms of PKC-Dependent Na⁺K⁺ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

et al. 2007

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“…The protocol was approved by the local Committee for Animal Research. Renal insufficiency was produced by suppressing a major portion of renal tissue, as described (2). Briefly, the left kidney was dipped in hot water for 14 s to burn the outer cortex.…”

Section: Methodsmentioning

confidence: 99%

“…Thus Bertuccio et al (1,2) showed an increase in intracellular cAMP levels in microdissected mTAL segments in chronic renal failure (CRF) rats, which were unresponsive to VP in vitro, opposed to baseline lower levels and a dose-response stimulation in control animals (1,2). Alternatively, Kwon et al (16) demonstrated compensatory increases in Na ϩ -K ϩ -Cl Ϫ cotransport expression per nephron in distal segments of the remnant kidney model (16).…”

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confidence: 99%

Endogenous vasopressin regulates Na-K-ATPase and Na⁺-K⁺-Cl⁻cotransporterrbsc-1in rat outer medulla

Bertuccio

Ibarra

Toledo

et al. 2002

American Journal of Physiology-Renal Physiology

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Previous reports have shown a stimulatory effect of vasopressin (VP) on Na-K-ATPase and rBSC-1 expression and activity. Whether these VP-dependent mechanisms are operating in vivo in physiological conditions as well as in chronic renal failure (CRF) has been less well studied. We measured ATPase expression and activity and rBSC-1 expression in the outer medulla of controls and moderate CRF rats both before and under in vivo inhibition of VP by OPC-31260, a selective V 2-receptor antagonist. OPC-31260 decreased Na-K-ATPase activity from 11.2 Ϯ 1.5 to 3.7 Ϯ 0.8 in controls (P Ͻ 0.05) and from 19.0 Ϯ 0.8 to 2.9 Ϯ 0.5 mol P i ⅐ mg protein Ϫ1 ⅐ h Ϫ1 in moderate CRF rats (P Ͻ 0.05). CRF was associated with a significant increase in Na-K-ATPase activity (P Ͻ 0.05). Similarly, CRF was also associated with a significant increase in Na-K-ATPase expression to 164.4 Ϯ 21.5% compared with controls (P Ͻ 0.05), and OPC-31260 decreased Na-K-ATPase expression in both controls and CRF rats to 57.6 Ϯ 9.5 and 105.3 Ϯ 10.9%, respectively (P Ͻ 0.05). On the other hand, OPC-31260 decreased rBSC-I expression in both controls and CRF rats to 60.8 Ϯ 6.5 and 30.0 Ϯ 6.9%, respectively (P Ͻ 0.05), and was not influenced by CRF (95.7 Ϯ 5.2%). We conclude that 1) endogenous VP modulated Na-K-ATPase and rBSC-1 in both controls and CRF; and 2) CRF was associated with increased activity and expression of the Na-K-ATPase in the outer medulla, in contrast to the unaltered expression of the rBSC-1. The data suggest that endogenous VP could participate in the regulation of electrolyte transport at the level of the outer medulla.vasopressin; rbsc-1; sodium-potassium-adenosine 5Ј-triphosphatase; chronic renal failure THERE IS STRONG EVIDENCE that vasopressin (VP) stimulates Na-K-ATPase and Na ϩ -K ϩ -Cl Ϫ cotransporter in the kidney outer medulla and, more precisely, in the medullary thick ascending limb of Henle (mTAL) (15). However, the experimental designs so far have been mostly related to the administration of exogenous VP, to either intact animals or in vitro preparations. The question of whether the level of endogenous VP activity plays a homeostatic role at the kidney outer medulla has not yet been examined. The introduction of powerful VP inhibitors has made it possible to design experiments looking at that question. OPC-31260 is a nonpeptide V 2 -receptor inhibitor developed by Yamamura et al. (21), and its actions are limited to states where VP activity is present. This approach was recently used by Ohara et al. (18), who were able to show a VP-mediated upregulation of the aquaporin-2 water channel in pregnant rats by using OPC-31260.In addition, previous experiments from our laboratory and those of others have suggested that in chronic renal failure the remaining nephrons suffer diverse adaptive mechanisms. Thus Bertuccio et al. (1, 2) showed an increase in intracellular cAMP levels in microdissected mTAL segments in chronic renal failure (CRF) rats, which were unresponsive to VP in vitro, opposed to baseline lower levels and a dose-respon...

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Mechanisms of Na + -K + -ATPase phosphorylation by PKC in the medullary thick ascending limb of Henle in the rat

Bertuccio

Cheng

Arrizurieta

et al. 2003

Pfl�gers Archiv European Journal of Physiology

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Sodium transport correlates with varying Na+-K+-ATPase activity rates along the nephron. Whether differences in Na+-K+-ATPase regulation by protein kinase C-dependent phosphorylation are also present has not been tested. We measured the degree of Na+-K+-ATPase alpha1 subunit phosphorylation by the binding of McK-1 antibody to dephosphorylated Ser-23 and Na+-K+-ATPase activity in medullary thick ascending limb of Henle (mTAL) and proximal tubules (PCT). The degree of Na+-K+-ATPase phosphorylation at Ser-23 was lower in mTAL than in PCT (DU 13.43+/-1.99 versus 2.3+/-0.20, respectively, P<0.01) while Na+-K+-ATPase activity was higher in mTAL (3,402+/-83 vs 711+/-158 pmol/mm tubule per hour in PCT, P<0.01). PKC inhibitor RO-318220 10(-6) M decreased phosphorylation in PCT to 125+/-10% ( P<0.05). In mTAL, RO-318220 did not modify the phosphorylation degree or the activity of Na+-K+-ATPase. Both calcineurin inhibitor FK-506 10(-6) M and phorbol 12-myristate 13-acetate (PMA) 10(-6) M increased the degree of Na+-K+-ATPase phosphorylation ( P<0.05) and inhibited Na+-K+-ATPase activity to 657+/-152 and 1,448+/-347 pmol/mm tubule per hour, respectively, in mTAL ( P<0.01). Increase in [Na+]i to 30, 50 and 70 mM resulted in no changes in Na+-K+-ATPase phosphorylation degree or activity in mTAL. Conversely, in PCT increments in [Na+]i were paralleled by decreased phosphorylation (from 120+/-7 to 160+/-15% of controls, P<0.05) and increased Na+-K+-ATPase activity (from 850+/-139 to 1,874+/-203 pmol/mm tubule per hour, P<0.01). Dopamine (DA) 10(-6) M decreased both Na+-K+-ATPase dephosphorylation to 41.85+/-9.58% ( P<0.05) and Na+-K+-ATPase activity to 2,405+/-176 pmol/mm tubule per hour in mTAL ( P<0.01). RO-318220 reversed DA effects. Data suggest that regulation of the degree of Na+-K+-ATPase alpha1 subunit phosphorylation at Ser-23 and enzyme activity have different mechanisms in mTAL than in PCT, and may help us to understand the physiological heterogeneity of both segments.

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Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure

Cited by 3 publications

References 23 publications

Mechanisms of PKC-Dependent Na⁺K⁺ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

Mechanisms of PKC-Dependent Na⁺K⁺ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

Endogenous vasopressin regulates Na-K-ATPase and Na⁺-K⁺-Cl⁻cotransporterrbsc-1in rat outer medulla

Mechanisms of Na + -K + -ATPase phosphorylation by PKC in the medullary thick ascending limb of Henle in the rat

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Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure

Cited by 3 publications

References 23 publications

Mechanisms of PKC-Dependent Na+K+ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

Mechanisms of PKC-Dependent Na+K+ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

Endogenous vasopressin regulates Na-K-ATPase and Na+-K+-Cl−cotransporterrbsc-1in rat outer medulla

Mechanisms of Na + -K + -ATPase phosphorylation by PKC in the medullary thick ascending limb of Henle in the rat

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Mechanisms of PKC-Dependent Na⁺K⁺ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

Mechanisms of PKC-Dependent Na⁺K⁺ATPase Phosphorylation in the Rat Kidney with Chronic Renal Failure

Endogenous vasopressin regulates Na-K-ATPase and Na⁺-K⁺-Cl⁻cotransporterrbsc-1in rat outer medulla