PMID- 20097874
OWN - NLM
STAT- MEDLINE
DCOM- 20100721
LR  - 20211020
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 24
IP  - 6
DP  - 2010 Jun
TI  - Dietary Na+ inhibits the open probability of the epithelial sodium channel in the 
      kidney by enhancing apical P2Y2-receptor tone.
PG  - 2056-65
LID - 10.1096/fj.09-151506 [doi]
AB  - Apical release of ATP and UTP can activate P2Y(2) receptors in the 
      aldosterone-sensitive distal nephron (ASDN) and inhibit the open probability 
      (P(o)) of the epithelial sodium channel (ENaC). Little is known, however, about 
      the regulation and physiological relevance of this system. Patch-clamp studies in 
      freshly isolated ASDN provide evidence that increased dietary Na(+) intake in 
      wild-type mice lowers ENaC P(o), consistent with a contribution to Na(+) 
      homeostasis, and is associated with increased urinary concentrations of UTP and 
      the ATP hydrolytic product, ADP. Genetic deletion of P2Y(2) receptors in mice 
      (P2Y(2)(-/-); littermates to wild-type mice) or inhibition of apical P2Y-receptor 
      activation in wild-type mice prevents dietary Na(+)-induced lowering of ENaC 
      P(o). Although they lack suppression of ENaC P(o) by dietary NaCl, P2Y(2)(-/-) 
      mice do not exhibit NaCl-sensitive blood pressure, perhaps as a consequence of 
      compensatory down-regulation of aldosterone levels. Consistent with this 
      hypothesis, clamping mineralocorticoid activity at high levels unmasks greater 
      ENaC activity and NaCl sensitivity of blood pressure in P2Y(2)(-/-) mice. The 
      studies indicate a key role of the apical ATP/UTP-P2Y(2)-receptor system in the 
      inhibition of ENaC P(o) in the ASDN in response to an increase in Na(+) intake, 
      thereby contributing to NaCl homeostasis and blood pressure regulation.
FAU - Pochynyuk, Oleh
AU  - Pochynyuk O
AD  - Department of Physiology, University of Texas Health Science Center, San Antonio, 
      Texas, USA.
FAU - Rieg, Timo
AU  - Rieg T
FAU - Bugaj, Vladislav
AU  - Bugaj V
FAU - Schroth, Jana
AU  - Schroth J
FAU - Fridman, Alla
AU  - Fridman A
FAU - Boss, Gerry R
AU  - Boss GR
FAU - Insel, Paul A
AU  - Insel PA
FAU - Stockand, James D
AU  - Stockand JD
FAU - Vallon, Volker
AU  - Vallon V
LA  - eng
GR  - R01 DK028602/DK/NIDDK NIH HHS/United States
GR  - R01 DK059594/DK/NIDDK NIH HHS/United States
GR  - R01 DK056248/DK/NIDDK NIH HHS/United States
GR  - P30 DK079337/DK/NIDDK NIH HHS/United States
GR  - R01 GM066232/GM/NIGMS NIH HHS/United States
GR  - R01GM66232/GM/NIGMS NIH HHS/United States
GR  - P30DK079337/DK/NIDDK NIH HHS/United States
GR  - R01DK59594/DK/NIDDK NIH HHS/United States
GR  - R01DK28602/DK/NIDDK NIH HHS/United States
GR  - R01DK56248/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100122
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Mineralocorticoids)
RN  - 0 (P2ry2 protein, mouse)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 0 (Sodium, Dietary)
RN  - 4964P6T9RB (Aldosterone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - UT0S826Z60 (Uridine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/urine
MH  - Aldosterone/pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cells, Cultured
MH  - Electrophysiology
MH  - Epithelial Sodium Channels/*metabolism
MH  - Homeostasis/drug effects
MH  - Kidney/cytology/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mineralocorticoids/pharmacology
MH  - Nephrons/cytology/drug effects/metabolism
MH  - Patch-Clamp Techniques
MH  - Receptors, Purinergic P2/*physiology
MH  - Receptors, Purinergic P2Y2
MH  - Signal Transduction
MH  - Sodium, Dietary/*administration & dosage/*pharmacology
MH  - Uridine Triphosphate/urine
PMC - PMC2874475
EDAT- 2010/01/26 06:00
MHDA- 2010/07/22 06:00
PMCR- 2011/06/01
CRDT- 2010/01/26 06:00
PHST- 2010/01/26 06:00 [entrez]
PHST- 2010/01/26 06:00 [pubmed]
PHST- 2010/07/22 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - fj.09-151506 [pii]
AID - 09-151506 [pii]
AID - 10.1096/fj.09-151506 [doi]
PST - ppublish
SO  - FASEB J. 2010 Jun;24(6):2056-65. doi: 10.1096/fj.09-151506. Epub 2010 Jan 22.