Abstract
Angiotensin II (AngII) is a potent regulator of electrolyte transport with biphasic effects on salt and HCO3-resorption in proximal tubule epithelia (PCT). In cultured PCT cells, pM to nM AngII activates a GTP-binding protein to inhibit cAMP formation and thus releases inhibition of apical Na/H exchange. Phospholipase A2 is activated by nM to μM AngII releasing arachidonate which is metabolized by a novel P450 epoxygenase to form 5,6-epoxy-eicosatrienoic acid (5,6-EET). 5,6-EET and nM apical AngII cause dihydropyridine-sensitive Ca2+ influx from the extracellular space, inhibition of apical-to-basolateral Na flux, and decrease in epithelial monolayer short circuit current. 5,6-EET also inhibits Na/K-ATPase by 50%. This P450 epoxygenase is physiologically important in the AngII-signaling system because the P450 inhibitor ketoconazole blocks AngII effects while potentiating exogenous 5,6-EET effects. Finally, these AngII-mediated signaling systems are polarized in the PCT with pM basolateral AngII inhibiting adenylate cyclase and nM apical AngII activating PLA2 and subsequent generation of 5,6-EET.
Original language | English (US) |
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Pages (from-to) | 199-207 |
Number of pages | 9 |
Journal | Renal Physiology and Biochemistry |
Volume | 14 |
Issue number | 4-5 |
State | Published - 1991 |
Keywords
- 5,6-EET
- Na transport
- P450 epoxygenase
- angiotensin II
- arachidonic acid
- cAMP
- calcium
- cell culture
- epithelial electrolyte transport
- metabolism
- proximal tubule
ASJC Scopus subject areas
- Physiology
- Nephrology