Nucleotides regulate nacl transport in mimcd-k2 cells via p2x and
p2y purinergic receptors.
McCoy, David E., Amanda L. Taylor, Brian A. Kudlow, Katherine Karlson,
Margaret J. Slattery, Lisa M. Schwiebert, Erik M. Schwiebert and
Bruce A. Stanton.
1Department of Physiology, Dartmouth Medical School, Hanover, NH
and 2Department of Physiology and Biophysics, University of Alabama
at Birmingham, Birmingham, AL
APStracts 6:0114F, 1999.
Extracellular nucleotides regulate NaCl transport in some epithelia.
However, the effects of nucleotide agonists on NaCl transport in the
renal inner medullary collecting duct (IMCD) are not known. The
objective of the present study was to determine if ATP and related
nucleotides regulate NaCl transport across mouse IMCD cell line
(mIMCD-K2) epithelial monolayers and, if so, via what purinergic
receptor subtypes. ATP and UTP inhibited Na- absorption (IscNa-) and
stimulated Cl- secretion (IscCl-). Using selective P2 agonists, we
report that P2X and P2Y purinoceptors regulate IscNa- and IscCl-. By
RT-PCR, two P2X receptor channels (P2X3, P2X4) and two P2Y G-protein
-coupled receptors (P2Y1, P2Y2) were identified. Functional
localization of P2 purinoceptors suggest that IscCl- is stimulated by
apical membrane-resident P2Y purinoceptors and P2X receptor channels,
whereas IscNa- is inhibited by apical membrane-resident P2Y
purinoceptors and P2X receptor channels. Taken together, we conclude
that nucleotide agonists inhibit IscNa- across mIMCD-K2 monolayers
through interactions with P2X and P2Y purinoceptors expressed on the
apical plasma membrane, whereas extracellular nucleotides stimulate
IscCl- through interactions with P2X and P2Y purinoceptors expressed
on the apical plasma membrane.
Received 26 March 1998; accepted in final form 4 June 1999.
APS Manuscript Number F073-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999