Extracellular Adenosine Stimulates Vacuolar ATPase-Dependent Proton Secretion in Medullary Intercalated Cells.

Autor:	Battistone MA; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Nair AV; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Barton CR; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Liberman RN; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Peralta MA; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Capen DE; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Brown D; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Breton S; Program in Membrane Biology, Center for Systems Biology, Nephrology Division, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts Breton.sylvie@mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2018 Feb; Vol. 29 (2), pp. 545-556. Date of Electronic Publication: 2017 Dec 08.
DOI:	10.1681/ASN.2017060643
Abstrakt:	Acidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H + -ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H + secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration-approved drug, but very little is known about the effect of adenosine on IC function. Therefore, we investigated the role of adenosine in the regulation of V-ATPase in ICs. Intravenous treatment of mice with adenosine or agonists of ADORA2A and ADORA2B purinergic P1 receptors induced V-ATPase apical membrane accumulation in medullary A-ICs but not in cortical A-ICs or other IC subtypes. Both receptors are located in A-IC apical membranes, and adenosine injection increased urine adenosine concentration and decreased urine pH. Cell fractionation showed that adenosine or an ADORA2A or ADORA2B agonist induced V-ATPase translocation from vesicles to the plasma membrane and increased protein kinase A (PKA)-dependent protein phosphorylation in purified medullary ICs that were isolated from mice. Either ADORA2A or ADORA2B antagonists or the PKA inhibitor mPKI blocked these effects. Finally, a fluorescence pH assay showed that adenosine activates V-ATPase in isolated medullary ICs. Our study shows that medullary A-ICs respond to luminal adenosine through ADORA2A and ADORA2B receptors in a cAMP/PKA pathway-dependent mechanism to induce V-ATPase-dependent H + secretion. (Copyright © 2018 by the American Society of Nephrology.)
Databáze:	MEDLINE
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