Biphasic regulation of renal proximal bicarbonate absorption by luminal AT(1A) receptor.
Angiotensin II (AngII) regulates renal proximal transport in a biphasic way. It has been recently shown that the basolateral type 1A receptor (AT(1A)) mediates the biphasic regulation of Na(+)-HCO(3)(-) cotransporter (NBC) by AngII. However, the receptor subtype(s) responsible for the luminal AngII actions remained to be established. To clarify this issue, the luminal AngII effects in isolated proximal tubules from wild-type (WT) and AT(1A)-deficient mice (AT(1A) KO) were compared. In WT, the rate of bicarbonate absorption (JHCO(3)(-)), analyzed with a stop-flow microspectrofluorometric method, was stimulated by 10(-10) mol/L luminal AngII but was inhibited by 10(-6) mol/L luminal AngII. Both stimulatory and inhibitory effects of AngII were completely blocked by valsartan (AT(1) antagonist) but unaffected by PD 123,319 (AT(2) antagonist). In AT(1A) KO, in contrast, luminal AngII (10(-10) - 10(-6) mol/L) did not change JHCO(3)(-). In WT, 10(-6) mol/L luminal AngII increased cell Ca(2+) concentrations ([Ca(2+)](i)), which was again blocked by valsartan but not by PD 123,319. However, luminal AngII did not increase [Ca(2+)](i) in AT(1A) KO. On the other hand, the addition of arachidonic acid similarly inhibited JHCO(3)(-) in WT and AT(1A) KO. Furthermore, the acute activation of protein kinase C by phorbol 12-myristate 13-acetate similarly stimulated JHCO(3)(-) in WT and AT1A KO, indicating that the inhibitory and stimulatory pathways necessary for the AngII actions were preserved in AT(1A) KO. These results indicate that the luminal AT(1A) mediates the biphasic regulation of bicarbonate absorption by luminal AngII, while no evidence was obtained for a role of AT(2).
Zheng
Yanan
Y
Department of Internal Medicine, Faculty of Medicine, Tokyo University, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Horita
Shoko
S
Hara
Chiaki
C
Kunimi
Motoei
M
Yamada
Hideomi
H
Sugaya
Takeshi
T
Goto
Atsuo
A
Fujita
Toshiro
T
Seki
George
G
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001639:Bicarbonates; D002273:Carcinogens; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016718:Arachidonic Acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium