Wiederkehr, M R; Di Sole, F; Collazo, R; Quiñones, H; Fan, L; Murer, H; Helmle-Kolb, C; Moe, O W (2001). Characterization of acute inhibition of Na/H exchanger NHE-3 by dopamine in opossum kidney cells. Kidney International, 59(1):197-209.
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BACKGROUND: Dopamine (DA) is a principal natriuretic hormone that defends extracellular fluid volume from a Na load. Natriuresis is effected partly through inhibiting the proximal tubule Na/H exchanger NHE-3. Changes in NHE-3 phosphorylation is one mechanism by which NHE-3 activity is regulated. METHODS: We used opossum kidney (OK) cells to characterize the differential and synergistic effects of DA receptor subtype-1 (DA1) and -2 (DA2) agonists and the effect of blockade of protein kinase A (PKA) or protein kinase C (PKC) on NHE-3 activity and phosphorylation. RESULTS: DA and DA1 agonists inhibited NHE-3 activity, and DA1 antagonist blocked the effect of either DA or DA1 agonist. DA2 agonist alone had no effect, but DA2 antagonist reduced the DA effect on NHE-3 activity. DA1 and DA2 agonists together were more potent than DA1 alone. PKA inhibition eliminated the effect of DA1 agonist and partially blocked the effect of DA on NHE-3 activity. PKC inhibition did not block the DA effect. DA1 agonist and PKA activation phosphorylated NHE-3 on identical sites. Despite lack of effect on NHE-3 activity, DA2 agonists increased NHE-3 phosphorylation. DA-induced NHE-3 phosphorylation was distinct from DA1 and PKA but closely resembled DA2. CONCLUSION: 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.
|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > Institute of Physiology|
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
|Date:||1 January 2001|
|Deposited On:||11 Feb 2008 12:22|
|Last Modified:||28 Nov 2013 00:46|
|Publisher:||Nature Publishing Group|
|Citations:||Web of Science®. Times Cited: 35|
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