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: Differential activation of the HCO(3)(-) conductance through the cystic fibrosis transmembrane conductance regulator anion channel by genistein and forskolin in murine duodenum.
    Author: Tuo B, Wen G, Seidler U.
    Journal: Br J Pharmacol; 2009 Nov; 158(5):1313-21. PubMed ID: 19788494.
    Abstract:
    BACKGROUND AND PURPOSE: Many cystic fibrosis (CF)-associated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channels affect CFTR-activated HCO(3)(-) transport more than Cl(-) transport. Targeting the CFTR HCO(3)(-) conductance, if possible, may therefore be of major therapeutic benefit. In the present study, we examined the effects of genistein and forskolin on duodenal mucosal HCO(3)(-) and Cl(-) secretion. EXPERIMENTAL APPROACH: Murine duodenal mucosal HCO(3)(-) and Cl(-) secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (I(sc)) techniques. KEY RESULTS: Genistein markedly stimulated duodenal HCO(3)(-) secretion and I(sc) in a dose-dependent manner in CFTR wild-type mice, but not in CFTR null mice. CFTR(inh)-172, a highly specific CFTR inhibitor, inhibited genistein-stimulated duodenal HCO(3)(-) secretion and I(sc) in wild-type mice. Genistein induced 59% net HCO(3)(-) increase and 123% net I(sc) increase over basal value, whereas forskolin, an activator of adenylate cyclase, induced 94% net HCO(3)(-) increase and 507% net I(sc) increase, indicating that, compared with forskolin, genistein induced a relatively high HCO(3)(-)/I(sc) ratio. Further data showed that CFTR HCO(3)(-)/Cl(-) conductance ratio was 1.05 after genistein stimulation, whereas after forskolin stimulation, the CFTR HCO(3)(-)/Cl(-) conductance ratio was 0.27. CONCLUSIONS AND IMPLICATIONS: Genistein stimulates duodenal HCO(3)(-) and Cl(-) secretion through CFTR, and has a relatively high selectivity for the CFTR HCO(3)(-) conductance, compared with forskolin. This may indicate the feasibility of selective targeting of the HCO(3)(-) conductance of the CFTR channels.
    [Abstract] [Full Text] [Related] [New Search]