These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Protein kinase C-mediated up-regulation of Na+/Ca2+-exchanger in rat hepatocytes determined by a new Na+/Ca2+-exchanger inhibitor, KB-R7943.
    Author: Ikari A, Sakai H, Takeguchi N.
    Journal: Eur J Pharmacol; 1998 Oct 30; 360(1):91-8. PubMed ID: 9845277.
    Abstract:
    The regulatory mechanism of the plasma membrane Na+/Ca2+-exchanger in isolated rat hepatocytes was studied using microspectrofluorometry and 45Ca2+ uptake methods. Exposure of single hepatocytes to low-Na+ solutions induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) which depended on the presence of extracellular Ca2+. 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate (KB-R7943), a novel selective inhibitor of Na+/Ca2+-exchangers, inhibited the initial rate of [Ca2+]i increase induced by exposure to the low-Na+ solution (IC50 = 2 microM). KB-R7943 also reduced the initial rate of 45Ca2+ uptake (IC50 = 4 microM). The increase in [Ca2+]i induced by exposure to the low-Na+ solution was inhibited by pre-incubation with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 50 microM), but not with N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8, 60 microM) or a tyrosine kinase inhibitor, genistein (100 microM). Furthermore, taurocholate and phorbol-12,13-dibutyrate, both of which activate protein kinase C, promoted the increase in [Ca2+]i. These [Ca2+]i increases were sensitive to KB-R7943. Our results indicate that the Na+/Ca2+-exchanger is up-regulated via protein kinase C. The activity of Na+/Ca2+-exchangers is not evident under normal physiological conditions, suggesting that the exchanger may be activated under pathophysiological conditions.
    [Abstract] [Full Text] [Related] [New Search]