Molecular Pharmacology, Vol 14, 357-365, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Responses of Fetal Rat Bones to Solanum malacoxylon in Vitro: a Possible Explanation of Previous Paradoxical Results

¹ Department of Pharmacology, Northwestern University, Chicago, Illinois 60611
² Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706

A partially purified extract of Solanum malacoxylon was tested for its actions on fetal rat bone in vitro. The extract had a biphasic effect on bone resorption in vitro, stimulating at low concentrations (0.3-0.3 mg/ml) and inhibiting at concentrations of 1 mg/ml and higher. The stimulatory effect could be antagonized with calcitonin or glucagon. At a concentration of 1.0 mg/ml, the S. malacoxylon extract antagonized the bone-resorbing effects of l,25-dihydroxyvitamin D₃[1,25-(OH)₂D₃] and parathyroid hormone. To determine whether effects in vitro could be due to 1,25-(OH)₂D₃ released into the medium during incubation, bones were cultured with equieffective concentrations of parathyroid hormone, 1,25-(OH)₂D₃, or S. malacoxylon, and the culture medium was extracted with organic solvents. Chloroform or benzene extracts from control or parathyroid hormone treated cultures were inactive, whereas those from 1,25-(OH)₂D₃-treated cultures retained most or all of the activity of the original media. Benzene extracts of S. malacoxylon culture, media inhibited resorption. The inhibitory material could be removed by high-pressure liquid chromatography, but the benzene extract was still ineffective. The results would be consistent with S. malacoxylon acting in vitro as the unhydrolyzed glycoside conjugate. However, it is also possible that the bone cells hydrolyze the glycoside to release small amounts of 1,25-(OH)₂D₃, which then interacts with the receptor.

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ACKNOWLEDGMENTS We would like to express our appreciation to Jan Miller and Thalia Mavreas for their excellent technical assistance, and to Lorraine Reeve and Michael Holick for providing the S. malacoxylon extract used in these studies.