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Regulatory Mechanisms of Angiotensin II on the $Na^+/H^+$ Antiport System in Rabbit Renal Proximal Tubule Cells. I. Stimulatory Effects of ANG II on $Na^+$ Uptake

Han, Ho-Jae   (Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National UniversityUU0001112  ); Koh, Hyun-Ju   (Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National UniversityUU0001112  ); Park, Soo-Hyun   (Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National UniversityUU0001112  );
  • 초록

    The importance of the kidney in the development of hypertension was first demonstrated by Goldblatt and his colleagues more than fifty years ago. Many hormones and other regulatory factors have been proposed to play a major role in the development of hypertension. Among these factors angiotensia II (ANG II) is closely involved in renal hypertension development since it directly regulates $Na^+$ reabsorption in the renal proximal tubule. Thus the aim of the present study was to examine signaling pathways of low dose of ANC II on the $Na^+$ uptake of primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined seum-free medium. The results were as follows: 1) $10^{-11}$ M ANG II has a significant stimulatory effect on growth as compared with control. Alkaline phosphatase exhibited significantly increased activity. However, leucine aminopeptidase and ${\gamma}-glutamyl$ transpeptidase activity were not significant as compared with control. In contrast to $10^{-11}$ M ANG II stimulated $Na^+$ uptake $(108.03{\pm}2.16% of that of control)$ , $10^{-9}$ M ANG II inhibited ( $92.42{\mu}2.23%$ of that of control). The stimulatory effect of ANG II on $Na^+$ uptake was amiloride-sensitive and inhibited by losartan (ANG II receptor subtype 1 antagonist) and not by PD123319 (ANG II receptor subtype 2 antagonist). 2) Pertussis toxin (PTX) alone inhibited $Na^+$ uptake by $85.52{\pm}3.52%$ of that of control. In addition, PTX pretreatment prevented the AMG II-induced stimulation of $Na^+$ uptake. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), forskolin, and isobutylmethylxanthine (IBMX) alone inhibited $Na^+$ uptake by $88.79{\pm}2.56,\;80.63{\pm}4.38,\;and\;84.47{\pm}4.74%$ of that of control, respectively, and prevented the ANG II-induced stimulation of $Na^+$ uptake. However, $10^{-11}$ M ANG II did not stimulate cAMP production. 3) The addition of 12-O-te-tradecanoylphorbol-13-acetate (TPA, 0.01 ng/ml) to the PTCs produced significant increase in $Na^+$ uptake ( $114.43{\pm}4.05%$ of that of control). When ANG II and TPA were added together to the PTCs, there was no additive effect on $Na^+$ uptake. Staurosporine alone had no effect on $Na^+$ uptake, but led to a complete inhibition of ANG II- or TPA-induced stimulation of Na'uptake. ANG II treatment resulted in a $111.83{\mu}4.51%$ increase in total protein kinase C (PKC) activity. In conclusion, the PTX-sensitive PKC pathway is the main signaling cascade involved in the stimulatory effects of ANG II on $Na^+$ uptake in the PTCs.


  • 주제어

    Kidney .   Angiotensin II .   $Na^+/H^+$ antiporter .   cAMP .   PKC.  

 저자의 다른 논문

  • Koh, Hyun-Ju (4)

    1. 1997 "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" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 (4): 425~434    
    2. 1998 "초대배양한 신장 근위세뇨관세포에서 ANG II의 Na+ uptake 촉진효과에 대한 dopamine의 효과" 大韓獸醫學會誌 = Korean journal of veterinary research 38 (3): 518~524    
    3. 1998 "초대배양한 토끼 신장 근위세뇨관세포의 Na+ uptake에 대한 norepinephrine 과 angiotensin II의 상호작용" 大韓獸醫學會誌 = Korean journal of veterinary research 38 (3): 525~534    
    4. 1999 "The Roles of Arachidonic Acid and Calcium in the Angiotensin II-induced Inhibition of $Na^+$ Uptake in Renal Proximal Tubule Cells" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 (1): 83~91    

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