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

• 영문명: 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
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Ho Jae Han Soo Hyun Park Hyun Ju Koh
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제1권 제4호, 425~434쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1997.01.01

영문 초록

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^-9 M) inhibited Na⁺ uptake and increased [Ca²⁺]_i level in the PTCs. However, low concentrations of (＜10^-11 ANG II) stimulated Na⁺ uptake and did not affect [Ca²⁺]_i level. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis(β-amino ethyl ether)-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% of that of ANG II, 81.85⁑1.84% of that of BK). 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^-6 M) and AACOCF₃ (10^-5 M) for 1 hr before the addition of 10^-9 M ANG II, the inhibitory effect of ANG II was reversed. In addition, econazole (10^-6 M) 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.

키워드

Kidney Angiotensin II Na⁺/H⁺ antiporter Ca²⁺