Kunzelmann, Karl and Bachhuber, T. and Regeer, R. and Markovich, D. and Sun, J. and Schreiber, R. (2004) Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2. FASEB JOURNAL, 18 (13). 142-+. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
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 coi-mmunoprecipitated the beta subunit of ENaC. ENaC was inhibited by ATP stimulation of P2Y(2) receptors in Xenopus oocytes. Mutations in the PIP2 binding domain of gammaENaC 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PIP2; TRANSMEMBRANE CONDUCTANCE REGULATOR; STIMULATED SODIUM-TRANSPORT; ATP CHANNEL INHIBITION; CYSTIC-FIBROSIS; A6 CELLS; EXTRACELLULAR NUCLEOTIDES; PHOSPHOLIPASE-C; ACTIVATION; BINDING; ENaC; phosphatidylinositol 4,5-bisphosphate; purinergic receptors; Na+ absorption; trachea |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jun 2021 08:05 |
| Last Modified: | 28 Jun 2021 08:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37111 |
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