PMID- 21075848
OWN - NLM
STAT- MEDLINE
DCOM- 20110302
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 2
DP  - 2011 Jan 14
TI  - Diminished paracrine regulation of the epithelial Na+ channel by purinergic 
      signaling in mice lacking connexin 30.
PG  - 1054-60
LID - 10.1074/jbc.M110.176552 [doi]
AB  - We tested whether ATP release through Connexin 30 (Cx30) is part of a local 
      purinergic regulatory system intrinsic to the aldosterone-sensitive distal 
      nephron (ASDN) important for proper control of sodium excretion; if changes in 
      sodium intake influence ATP release via Cx30; and if this allows a normal ENaC 
      response to changes in systemic sodium levels. In addition, we define the 
      consequences of disrupting ATP regulation of ENaC in Cx30(-/-) mice. Urinary ATP 
      levels in wild-type mice increase with sodium intake, being lower and less 
      dependent on sodium intake in Cx30(-/-) mice. Loss of inhibitory ATP regulation 
      causes ENaC activity to be greater in Cx30(-/-) versus wild-type mice, 
      particularly with high sodium intake. This results from compromised ATP release 
      rather than end-organ resistance: ENaC in Cx30(-/-) mice responds to exogenous 
      ATP. Thus, loss of paracrine ATP feedback regulation of ENaC in Cx30(-/-) mice 
      disrupts normal responses to changes in sodium intake. Consequently, ENaC is 
      hyperactive in Cx30(-/-) mice lowering sodium excretion particularly during 
      increases in sodium intake. Clamping mineralocorticoids high in Cx30(-/-) mice 
      fed a high sodium diet causes a marked decline in renal sodium excretion. This is 
      not the case in wild-type mice, which are capable of undergoing 
      aldosterone-escape. This loss of the ability of ENaC to respond to changes in 
      sodium levels contributes to salt-sensitive hypertension in Cx30(-/-) mice.
FAU - Mironova, Elena
AU  - Mironova E
AD  - Department of Physiology, University of Texas Health Science Center, San Antonia, 
      Texas 78229-3900, USA.
FAU - Peti-Peterdi, Janos
AU  - Peti-Peterdi J
FAU - Bugaj, Vladislav
AU  - Bugaj V
FAU - Stockand, James D
AU  - Stockand JD
LA  - eng
GR  - R01 DK059594/DK/NIDDK NIH HHS/United States
GR  - R01 DK064324/DK/NIDDK NIH HHS/United States
GR  - R01DK59594/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101112
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Connexin 30)
RN  - 0 (Connexins)
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Gjb6 protein, mouse)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 0 (Sodium Chloride, Dietary)
RN  - 4964P6T9RB (Aldosterone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/urine
MH  - Aldosterone/metabolism
MH  - Animals
MH  - Connexin 30
MH  - Connexins/*genetics/*metabolism
MH  - Epithelial Sodium Channels/*metabolism
MH  - Feedback, Physiological/physiology
MH  - Hypertension, Renal/genetics/*metabolism
MH  - Kidney Tubules, Collecting/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Paracrine Communication/*physiology
MH  - Receptors, Purinergic P2Y2/metabolism
MH  - Signal Transduction/physiology
MH  - Sodium Chloride, Dietary/pharmacology/urine
PMC - PMC3020712
EDAT- 2010/11/16 06:00
MHDA- 2011/03/03 06:00
PMCR- 2012/01/14
CRDT- 2010/11/16 06:00
PHST- 2010/11/16 06:00 [entrez]
PHST- 2010/11/16 06:00 [pubmed]
PHST- 2011/03/03 06:00 [medline]
PHST- 2012/01/14 00:00 [pmc-release]
AID - S0021-9258(20)56293-5 [pii]
AID - M110.176552 [pii]
AID - 10.1074/jbc.M110.176552 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Jan 14;286(2):1054-60. doi: 10.1074/jbc.M110.176552. Epub 2010 
      Nov 12.