Characterization of acute inhibition of Na/H exchanger NHE-3 by dopamine in opossum kidney cells

Wiederkehr, Michael R.; Sole, Francesca Di; Collazo, Roberto; Quiñones, Henry; Fan, Lingzhi; Murer, Heini; Helmle-Kolb, Corinna; Moe, Orson W.

doi:10.1046/j.1523-1755.2001.00480.x

Cited by 53 publications

(74 citation statements)

References 65 publications

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“…It has been previously reported that H89 fully or partially prevented the NHE inhibition induced by 8-Br-cAMP or by factors that increase intracellular cAMP levels (5,(26)(27)(28)(29). Therefore, we analyzed the effect of H89 on the PKA-and EPAC-dependent inhibitions.…”

Section: Resultsmentioning

confidence: 99%

“…This transporter is down-regulated by parathyroid hormone (PTH) and dopamine. Acute treatment of rats with PTH (2, 3) or short exposure of opossum kidney (OK) cells to PTH or dopamine (4,5) inhibits NHE3 activity without reducing its expression in the BBM. The renal type IIa Na ϩ -coupled inorganic phosphate cotransporter (NaPi-IIa; SLC34A1) is also expressed in the BBM of PT where it mediates the bulk of Pi reabsorption from primary urine (6).…”

Section: Regulation Of Sodium-proton Exchanger Isoform 3 (Nhe3) By Pkmentioning

confidence: 99%

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Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Honegger

Capuano

Winter

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The Na + /H + exchanger 3 (NHE3) is expressed in the brush border membrane (BBM) of proximal tubules (PT). Its activity is down-regulated on increases in intracellular cAMP levels. The aim of this study was to investigate the contribution of the protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC) dependent pathways in the regulation of NHE3 by adenosine 3′,5′-cyclic monophosphate (cAMP). Opossum kidney cells and murine kidney slices were treated with cAMP analogs, which selectively activate either PKA or EPAC. Activation of either pathway resulted in an inhibition of NHE3 activity. The EPAC-induced effect was independent of PKA as indicated by the lack of activation of the kinase and the insensitivity to the PKA inhibitor H89. Both PKA and EPAC inhibited NHE3 activity without inducing changes in the expression of the transporter in BBM. Activation of PKA, but not of EPAC, led to an increase of NHE3 phosphorylation. In contrast, activation of PKA, but not of EPAC, inhibited renal type IIa Na + -coupled inorganic phosphate cotransporter (NaPi-IIa), another Na-dependent transporter expressed in proximal BBM. PKA, but not EPAC, induced the retrieval of NaPi-IIa from BBM. Our results suggest that EPAC activation may represent a previously unrecognized mechanism involved in the cAMP regulation of NHE3, whereas regulation of NaPi-IIa is mediated by PKA but not by EPAC.

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Section: Resultsmentioning

confidence: 99%

Section: Regulation Of Sodium-proton Exchanger Isoform 3 (Nhe3) By Pkmentioning

confidence: 99%

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Honegger

Capuano

Winter

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…As illustrated in Figure 4A, activity changes under these conditions resembled that of cells examined for effect of 10 Ϫ6 M CPA alone. An analogue response pattern of NHE3 was seen with dopamine, which inhibits OK-NHE3 activity through a mechanism involving DR1 receptor-mediated PKA activation, whereas stimulation of DR2 receptors has an effect only on NHE3 phosphorylation (29). As depicted in Figure 4B, 10 Ϫ9 M CPA partially abrogated negative regulation elicited by 10 Ϫ5 M dopamine, whereas 10 Ϫ6 M CPA caused only a slight attenuation of the inhibitory effect of dopamine.…”

Section: Characterization Of Signaling Mechanism Accounting For the Smentioning

confidence: 87%

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Sole¹,

Cerull²,

Petzke³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Regulation of renal apical Na ϩ /H ϩ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na ϩ homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N 6 -cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations Ͼ10 Ϫ8 M inactivate NHE3, whereas concentrations Ͻ10 Ϫ8 M stimulate NHE3 activity. Acute CPA-induced control of NHE3 was blocked by antagonists of A 1 adenosine receptors and inhibition of phospholipase C, pretreatment with BAPTA-AM (chelator of cellular calcium), and exposure to pertussis toxin. Stimulatory and to some extent also inhibitory CPA concentrations attenuated 8-bromo-cAMP and dopaminemediated inhibition of NHE3. BAPTA eliminated the ability of a stimulatory dose of CPA to attenuate 8-bromo-cAMP-induced suppression of NHE3 activity. Upon inhibition of protein kinase C, CPA at an inhibitory dose provoked activation of NHE3, which is partially reverted by 8-bromo-cAMP and suppressed by pre-incubation with BAPTA-AM. Cytochalasin B, an actin-modifying agent, selectively prevented downregulation but did not affect upregulation of NHE3 activity by CPA. In conclusion, these observations demonstrate that (1) CPA modulates NHE3 activity by elevation of cellular Ca 2ϩ exerting a negative control on adenylate cyclase activity, (2) protein kinase C is the determining factor leading to CPAinduced downregulation of NHE3 activity, and (3) alterations of surface NHE3 abundance may contribute to A 1 adenosine receptor-dependent inhibition of NHE3 activity.

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“…We recently have shown that A 1 R-mediated inactivation of NHE3 is dependent on protein kinase C (PKC) (7,9). Phosphorylation of NHE3 is an early event in regulation of NHE3 by protein kinases (36,37,55,56). Elimination of phosphoserines on NHE3 may disrupt CPA regulation of NHE3 activity.…”

Section: Identification Of Structural Elements Required For Downregulmentioning

confidence: 99%

Acute Regulation of Na/H Exchanger NHE3 by Adenosine A1 Receptors Is Mediated by Calcineurin Homologous Protein

Sole

Cerull

Babich

et al. 2004

Journal of Biological Chemistry

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Characterization of acute inhibition of Na/H exchanger NHE-3 by dopamine in opossum kidney cells

Abstract: We postulate the following: (1) DA modifies NHE-3 phosphorylation by activating PKA through DA1 and by other kinases/phosphatases via DA2. (2) DA1 is sufficient to inhibit NHE-3, while DA2 is insufficient but plays a synergistic role by altering NHE-3 phosphorylation.

Cited by 53 publications

References 65 publications

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Acute Regulation of Na/H Exchanger NHE3 by Adenosine A1 Receptors Is Mediated by Calcineurin Homologous Protein

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