Korean J Physiol Pharmacol.
1999 Feb;3(1):83-91.
The roles of arachidonic acid and calcium in the angiotensin II-induced inhibition of Na+ uptake in renal proximal tubule cells
- Affiliations
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- 1College of Veterinary Medicine, Hormone Research Center, Kwangju 500-757 South Korea.
- 2Department of Human Nutrition & Food Science Chungnam Sanup University Hongsung 358-800 Korea.
- 3Department of Veterinary Medicine, Cheju National University, Cheju 690-756, Korea.
Abstract
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Angiotensin II (ANG II) has a biphasic effect on Na+ transport in
proximal tubule: low doses of ANG II increase the Na+ transport,
whereas high doses of ANG II inhibit it. However, the mechanisms of
high dose ANG II-induced inhibition on Na+ uptake are poorly
understood. Thus the aim of the present study was to investigate signal
transduction pathways involved in the ANG II-induced inhibition of Na+
uptake in the primary cultured rabbit renal proximal tubule cells
(PTCs) in hormonally defined serum-free medium. ANG II (10-9 M)-induced
inhibition of Na+ uptake was blocked by losartan (10-8 M, AT1
antagonist), but not by PD123319 (10-8 M, AT2 antagonist) (P < 0.05).
ANG II-induced inhibition of Na+ uptake was also completely abolished
by neomycin (10-4 M, PLC inhibitor), W-7 (10-4 M, calmodulin
antagonist), and AACOCF3 (10-6 M, PLA2 inhibitor) (P < 0.05). ANG II
significantly increased (3H)arachidonic acid (AA) release compared to
control. The ANG II-induced (3H)AA release was blocked by losartan,
AACOCF3, neomycin, and W-7, but not by PD123319. ANG II-induced (3H)AA
release in the presence of extracellular Ca2+ was greater than in
Ca2+-free medium, and it was partially blocked by TMB-8 (10-4 M,
intracelluar Ca2+ mobilization blocker). However, in the absence of
extracellular Ca2+, it was completely blocked by TMB-8. In addition,
econazole (10-6 M, cytochrome P-450 monooxygenase inhibitor) and
indomethacin (10-6 M, cyclooxygenase inhibitor) blocked ANG II-induced
inhibition of Na+ uptake, but NGDA (10-6 M, lipoxygenase inhibitor) did
not affect it. In conclusion, PLA2-mediated AA release is involved in
ANG II-induced inhibition of Na+ uptake and is modulated by (Ca2+)i in
the PTCs.