Inhibition of binding of basic fibroblast growth factor to low and high affinity receptors by carrageenans.
The effect of carrageenans, a family of polysulphated polysaccharides, on the binding of basic fibroblast growth factor (bFGF) to low affinity (heparin-like) receptors and high affinity receptors on baby hamster kidney cells was investigated. kappa-, iota-, and lambda-carrageenans all inhibited binding of bFGF to both types of receptors with iota-carrageenan being the most potent inhibitor (IC50 values of approx. 0.7 and 4 micrograms/mL for inhibition of binding to low and high affinity receptors respectively). Heparin reduced the inhibition of bFGF binding to high affinity receptors caused by iota-carrageenan. Heparin and iota-carrageenan were comparable in their activities at displacing pre-bound bFGF from both low affinity receptors and high affinity receptors. These results indicate that iota-carrageenan binds to the heparin-binding domain on bFGF and that this may be sufficient to reduce the ability of bFGF to bind to high affinity receptors.
Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Cambridge, U.K.
R
R
Hoffman
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D
Sykes
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002351:Carrageenan / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D002351:Carrageenan; D006493:Heparin