GM3 ganglioside inhibits endothelin-1-mediated signal transduction in C6 glioma cells

We found that sparse and confluent C6 glioma cells differ both in GM3 conte nt, which increases with cell density, and in endothelin-1 (ET-1)-induced p hosphoinositide hydrolysis, which was markedly higher in the sparse cells t han in the confluent. Also after manipulation of the cellular GM3 content t hrough treatment with exogenous GM3 or with drugs known to affect GM3 metab olism, the ET-I effect was inversely related to GM3 cellular levels. Cell t reatment with an anti-GM3 mAb resulted in the enhancement of ET-1-induced p hospholipase C activation and restored the capacity of GM3-treated cells to respond to ET-1. These findings suggest that the GM3 ganglioside represent s a physiological modulator of ET-1 signaling in glial cells. (C) 2001 Publ ished by Elsevier Science B.V. on behalf of the Federation of European Bioc hemical Societies.