Abstract
In OKP cells expressing ET(B) endothelin receptors, activation of Na+/H+ antiporter activity by endothelin-1 (ET-1) was resistant to low concentrations of ethylisopropyl amiloride, indicating regulation of Na+/H+ exchanger isoform 3 (NHE3). ET-1 increased NHE3 phosphorylation in cells expressing ET(B) receptors but not in cells expressing ET(A) receptors. Receptor specificity was not due to demonstrable differences in receptor- specific activation of tyrosine phosphorylation pathways or inhibition of adenylyl cyclase. Phosphorylation was associated with a decrease in mobility on SDS-PAGE, which was reversed by treating immunoprecipitated NHE3 with alkaline phosphatase. Phosphorylation was first seen at 5 min and was maximal at 15-30 min. Phosphorylation was maximal with 10-9 M ET-1. Phosphorylation occurred on threonine and serine residues at multiple sites. In summary, ET- 1 induces NHE3 phosphorylation in OKP cells on multiple threonine and serine residues. ET(B) receptor specificity, time course, and concentration dependence are all similar between ET-1-induced increases in NHE3 activity and phosphorylation, suggesting that phosphorylation plays a key role in activation.
Original language | English (US) |
---|---|
Pages (from-to) | C938-C945 |
Journal | American Journal of Physiology - Cell Physiology |
Volume | 276 |
Issue number | 4 45-4 |
DOIs | |
State | Published - 1999 |
Keywords
- Adenylyl cyclase
- Endothelin
- OKP cells
- Sodium/hydrogen antiporter
- Tyrosine kinases
ASJC Scopus subject areas
- Physiology
- Cell Biology