PMID- 15504951
OWN - NLM
STAT- MEDLINE
DCOM- 20051107
LR  - 20131121
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 19
IP  - 1
DP  - 2005 Jan
TI  - Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2.
PG  - 142-3
AB  - Stimulation of purinergic receptors inhibits amiloride-sensitive Na+ transport in 
      epithelial tissues by an unknown mechanism. Because previous studies excluded the 
      role of intracellular Ca2+ or protein kinase C, we examined whether purinergic 
      regulation of Na+ absorption occurs via hydrolysis of phospholipid such as 
      phosphatidylinositol-bisphosphates (PIP2). Inhibition of amiloride-sensitive 
      short-circuit currents (Isc-Amil) by adenine 5'-triphosphate (ATP) in native 
      tracheal epithelia and M1 collecting duct cells was suppressed by binding 
      neomycin to PIP2, and recovery from ATP inhibition was abolished by blocking 
      phosphatidylinositol-4-kinase or diacylglycerol kinase. Stimulation by ATP 
      depleted PIP2 from apical membranes, and PIP2 co-immunoprecipitated the beta 
      subunit of ENaC. ENaC was inhibited by ATP stimulation of P2Y2 receptors in 
      Xenopus oocytes. Mutations in the PIP2 binding domain of betaENaC but not 
      gammaENaC reduced ENaC currents without affecting surface expression. 
      Collectively, these data supply evidence for a novel and physiologically relevant 
      regulation of ENaC in epithelial tissues. Although surface expression is 
      controlled by its C terminus, N-terminal binding of betaENaC to PIP2 determines 
      channel activity.
FAU - Kunzelmann, K
AU  - Kunzelmann K
AD  - Institut fur Physiologie, Universitat Regensburg, Universitatsstrasse 31, 
      Regensburg, Germany.
FAU - Bachhuber, T
AU  - Bachhuber T
FAU - Regeer, R
AU  - Regeer R
FAU - Markovich, D
AU  - Markovich D
FAU - Sun, J
AU  - Sun J
FAU - Schreiber, R
AU  - Schreiber R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041025
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 (P2ry2 protein, mouse)
RN  - 0 (Peptides)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Receptors, Purinergic)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (Sodium Channels)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Epithelial Cells/chemistry/metabolism
MH  - Epithelial Sodium Channels
MH  - Hydrolysis
MH  - Kidney Tubules, Collecting/chemistry/cytology/metabolism
MH  - Mice
MH  - Oocytes/chemistry/metabolism
MH  - Patch-Clamp Techniques/methods
MH  - Peptides/metabolism
MH  - Phosphatidylinositol 4,5-Diphosphate/*metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Receptors, Purinergic/metabolism
MH  - Receptors, Purinergic P2
MH  - Receptors, Purinergic P2Y2
MH  - Sodium Channel Blockers/*pharmacology
MH  - Sodium Channels/biosynthesis/*metabolism
MH  - Trachea/chemistry/metabolism
MH  - Xenopus
EDAT- 2004/10/27 09:00
MHDA- 2005/11/08 09:00
CRDT- 2004/10/27 09:00
PHST- 2004/10/27 09:00 [pubmed]
PHST- 2005/11/08 09:00 [medline]
PHST- 2004/10/27 09:00 [entrez]
AID - 04-2314fje [pii]
AID - 10.1096/fj.04-2314fje [doi]
PST - ppublish
SO  - FASEB J. 2005 Jan;19(1):142-3. doi: 10.1096/fj.04-2314fje. Epub 2004 Oct 25.