Comparison of solanaceous glycoalkaloids-evoked Ca(2+) influx in different types of cultured cells.
The effects of the potato glycoalkaloids alpha-chaconine, alpha-solanine and tomatine on the intracellular free Ca(2+) concentration were studied in undifferentiated mouse neuroblastoma x rat glioma hybrid NG 108-15 cells, mouse-skin fibroblastoma L-929 cells and mouse Balb/3T3 cells by using the Ca(2+)-sensitive fluorescent dye Fura-2. In all cultured cells treated with the alkaloids the intracellular Ca(2+) concentrations were raised in a dose-dependent manner. The Ca(2+) influx evoked by alpha-chaconine could not be prevented by metal ions or by inhibitors of Ca(2+) transport across membranes such as voltage-operated channel antagonists, muscarinic and nicotinic antagonists, or Na(+) and K(+) channel blockers. The concentrations of alpha-chaconine, alpha-solanine and tomatine that gave half-maximal response (ED(50)) in NG 108-15 cells were 12.0, 72.0 and 1.8 mum, respectively. ED(50) values in L-929 cells were 10.2 mum for alpha-chaconine and 65 mum for alpha-solanine and in Balb/3T3 cells the ED(50) values were 9.5 mum for alpha-chaconine and 66 mum for alpha-solanine. These findings support the hypothesis that the alkaloid-evoked Ca(2+) influx is caused by destabilization of the cell membrane and attribute a more important role to alpha-chaconine than alpha-solanine in potato poisoning. Fluorescence measurement of the free Ca(2+) concentration in the cytoplasm therefore represents a useful tool for the evaluation of pharmacological properties of potato alkaloids in vitro.
Toyoda
M
M
National Institute of Hygienic Sciences, Kamiyoga, Setagaya-ku, Tokyo 158, Japan; Institute for Medical Chemistry, Veterinary Medical University, Linke Bahngasse 11, 1030 Vienna, Austria; Kitasato University, Kitasato, Sagamihara-shi, Kanagawa 228, Japan.
Rausch
W D
WD
Inoue
K
K
Ohno
Y
Y
Fujiyama
Y
Y
Takagi
K
K
Saito
Y
Y