Premium
EFFECTS OF TETRANDRINE AND CLOSELY RELATED BIS‐BENZYLISOQUINOLINE DERIVATIVES ON CYTOSOLIC Ca 2+ IN HUMAN LEUKAEMIC HL‐60 CELLS: A STRUCTURE‐ACTIVITY RELATIONSHIP STUDY
Author(s) -
Leung YukMan,
Berdik Mariana,
Kwan ChiuYin,
Loh TattTuck
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb01752.x
Subject(s) - tetrandrine , benzylisoquinoline , chemistry , thapsigargin , intracellular , stereochemistry , cytosol , alkaloid , microbiology and biotechnology , biochemistry , pharmacology , biology , enzyme , biosynthesis
SUMMARY 1. Previously it has been shown that tetrandrine (TET), a bis‐benzylisoquinoline alkaloid, isolated from a Chinese herb Stephania tetrandra , can block non‐voltage‐operated Ca 2+ entry activated by intracellular Ca 2+ store depletion induced by thapsigargin (TSG) and can release intracellular Ca 2+ in HL‐60 cells. The present study attempted to identify the chemical group(s) of the TET molecule responsible for these dual effects. The effects of TET and its closely related analogues, hernandezine (HER) and berbamine (BER), on Ca 2+ entry and Ca 2+ release were compared in fura‐2‐loaded HL‐60 cells. 2. Berbamine was much less potent (IC 50 = 200 μmol/L) than TET and HER (both IC 50 values = 25 μmol/L) in inhibiting Ca 2+ entry activated by TSG. Furthermore, at 100 μmol/L, BER was much less effective than TET and HER in suppressing TSG‐induced Mn 2+ entry. At 30‐100 μmol/L, BER was significantly less effective than both TET and HER in causing Ca 2+ release from internal stores. However, only BER was able to cause store depletion‐activated Ca 2+ entry (or the so‐called ‘capacitative Ca 2+ entry') upon Ca 2+ readmission. 3. Taken together, the data from this structure‐activity relationship study reveal that the‐OCH 3 group of one particular benzene ring of TET, which distinguishes TET from BER, in part produces the dual pharmacological actions of TET.