Angiotensin II actions in the rabbit proximal tubule. Angiotensin II mediated signaling mechanisms and electrolyte transport in the rabbit proximal tubule.
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 microM 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.
Romero
M F
MF
Department of Genetics, Case Western Reserve University, School of Medicine, Cleveland, Ohio.
Hopfer
U
U
Madhun
Z T
ZT
Zhou
W
W
Douglas
J G
JG
D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D004573:Electrolytes / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism; D015398:Signal Transduction
D004573:Electrolytes; D011945:Receptors, Angiotensin; D000804:Angiotensin II