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KMID : 0811719970010040425
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Korean Journal of Physiology & Pharmacology
1997 Volume.1 No. 4 p.425 ~ p.434
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Regulatory Mechanisms of Angiotensin Ⅱ on the Na＋/H＋ Antiport System in Rabbit Renal Proximal Tubule Cells. Ⅱ. Inhibitory Effects of ANG Ⅱ on Na＋ Uptake
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Ho Jae Han
Soo Hyun Park/Hyun Ju Koh
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Abstract
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Many reports represent that angiotensin II (ANG II) caused a dose dependent biphasic effects on fluid transport in the proximal tubule. However, respective roles of different signaling pathways in mediating these effects remain unsettled. The aim of the present study was to examine signaling pathways at high doses of ANG II on the Na+ uptake of primary cultured rabbit renal proximal tubule cells(PTCs) in hormonally defined serum-free medium. High concentrations of ANG II (>10?9M) inhibited Na+ uptake and increased [Ca2+]ilevel in the PTCs. However, low concentrations of (<10?11ANGII) stimulated Na+ uptake and did not affect [Ca2+]ilevel. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis(/beta?aminoethylether)?N,N,N′, N'-tetra acetic acid (EGTA), and nifedifine partially blocked the inhibitory effects of ANG II on Na+ uptake. When ANG II and bradykinin (BK) were treated together, Na+ uptake was further reduced (88.47±1.98. In addition, W-7 and KN-62 blocked the ANG II-induced inhibition of Na+ uptake. Arachidonic acid reduced Na+ uptake in a dose-dependent manner. When ANG II and arachidonic acid were treated together, inhibitory effects on Na+ uptake significantly exhibited greater reduction than that of each group, respectively. When PTCs were treated by mepacrine (10?6M) and AACOCF3 (10?5M) for 1 hr before the addition of (<10?9ANGII), the inhibitory effect of ANG II was reversed. In addition, econazole (>10?6M) blocked ANG II-induced inhibition of Na+ uptake. In conclusion, the [Ca2+]i (calcium-calmodulin-dependent kinase) and phospholipase A2(PLA2) metabolites are involved in the inhibitory effects of ANG II on Na+ uptake in the PTCs.
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KEYWORD
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Kidney, Angiotensin Ⅱ, Na＋/H＋ antiporter, Ca2＋,
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