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Effect of Mercuric Chloride on Angiotensin II-Induced Ca++ Transient in the Proximal Tubule of Rats

  • Hitoshi Endou
  • Kyu Yong Jung
Chapter
Part of the Rochester Series on Environmental Toxicity book series (RSET)

Abstract

Angiotensin II (AII) is a powerful agent in the regulation of renal functions, and possesses its receptor(s) within the kidney. The second messenger of AII is considered to be Ca++. Since mercuric chloride is one of nephrotoxic heavy metals, its effects on All-mediated signal transduction have been investigated.

Rat kidneys were treated with collagenase, and microdissection was made for isolating defined nephron segments. [Ca++]i was determined using fluorescent indicator fura-2. In the freshly isolated early proximal tubule (S1), All-induced [Ca++]i rise was biphasic, demonstrating the two peaks corresponding to the 10−11 and 10−7M. HgCl2 (10−10 – 10−8M) potentiated the [Ca++]i increase induced by AII (10−11M) in a dose dependent manner, up to the 10−9M HgCl2. A similar effect was observed with methylmercury. To determine the mechanism of stimulatory effect of HgCl2 on 10−11M AII-induced [Ca++]i increase, nephron segments were pretreated with propranolol (10−4M), a PLC inhibitor. This stimulatory effect of HgCl2 was completely inhibited by propranolol. Moreover, 10−4M propranolol completely blocked the stimulatory effect of HgCl2 on AII-mediated inositol 1,4,5-triphosphate (IP3) production.

This study suggests for the first time that mercurial compounds stimulates the [Ca++]i increment induced by AII, possibly through an activation of phospholipase C (PLC).

Keywords

Proximal Tubule Mercuric Chloride Nephron Segment Kidney Proximal Tubule Sustained Phase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Hitoshi Endou
    • 1
  • Kyu Yong Jung
    • 1
  1. 1.Department of Pharmacology, Faculty of MedicineThe University of TokyoBunkyo-ku, TokyoJapan

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