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Nucleotides downregulate aquaporin 2 via activation of apical P2 receptors.

Wildman, Scott S.P., Boone, Michelle, Peppiatt-Wildman, Claire M., Contreras-Sanz, Alberto, King, Brian F., Shirley, David G., Deen, Peter M. T., Unwin, Robert J. (2009) Nucleotides downregulate aquaporin 2 via activation of apical P2 receptors. Journal of the American Society of Nephrology, 20 (7). pp. 1480-1490. ISSN 1046-6673. E-ISSN 1533-3450. (doi:10.1681/ASN.2008070686) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

Vasopressin regulates water reabsorption in the collecting duct, but extracellular nucleotides modulate this regulation through incompletely understood mechanisms. We investigated these mechanisms using immortalized mouse collecting duct (mpkCCD) cells. Basolateral exposure to dDAVP induced AQP2 localization to the apical membrane, but co-treatment with ATP internalized AQP2. Because plasma membrane-bound P2 receptors (P2R) mediate the effects of extracellular nucleotides, we examined the abundance and localization of P2R in mpkCCD cells. In the absence of dDAVP, P2Y(1) and P2Y(4) receptors localized to the apical membrane, whereas P2X(2), P2X(4), P2X(5), P2X(7), P2Y(2), P2Y(11), and P2Y(12) receptors localized to the cytoplasm. dDAVP induced gene expression of P2X(1), which localized to the apical domain, and led to translocation of P2X(2) and P2Y(2) to the apical and basolateral membranes, respectively. In co-expression experiments, P2R activation decreased membrane AQP2 and AQP2-mediated water permeability in Xenopus oocytes expressing P2X(2), P2Y(2,) or P2Y(4) receptors, but not in oocytes expressing other P2R subtypes. In summary, these data suggest that AQP2-mediated water transport is downregulated not only by basolateral nucleotides, mediated by P2Y(2) receptors, but also by luminal nucleotides, mediated by P2X(2) and/or P2Y(4) receptors.

Item Type: Article
DOI/Identification number: 10.1681/ASN.2008070686
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 10 Dec 2015 14:53 UTC
Last Modified: 29 May 2019 16:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53056 (The current URI for this page, for reference purposes)
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