Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine
- Sandoz Research Institute, East Hanover, NJ (USA)
- Sandoz Forschungsinstitut, Vienna (Austria)
Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5{mu}M T in fibroblast incubation media was associated with increased ({sup 3}H)thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6{mu}M reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 {mu}M. Neither the uptake of ({sup 3}H)thymidine nor the specific binding of {sup 125}I-PDGF to fibroblast receptors was significantly affected by 10 {mu}M T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism.
- OSTI ID:
- 5030118
- Report Number(s):
- CONF-870644-; CODEN: FEPRA; TRN: 90-006994
- Journal Information:
- Federation Proceedings, Federation of American Societies for Experimental Biology; (USA), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA (USA), 7-11 Jun 1987; ISSN 0014-9446
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques