Ganglioside GM1 prevents and reverses toluene-induced increases in membrane fluidity and calcium levels in rat brain synaptosomes.
The effects of exposure to ganglioside GM1 and to toluene in vitro upon synaptosomal integrity have been examined using fluorescence polarization of two probes: 1-[4(trimethylamino)phenyl]-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) to measure membrane anisotropy, and the fluorescent indicator fura-2 to assay levels of cytosolic calcium [( Ca2+]i). The anisotropy of both TMA-DPH and DPH was decreased by toluene, implying increased membrane fluidity. The decrease in TMA-DPH but not in DPH anisotropy was prevented by pretreatment with GM1 in concentrations as low as 10 microM. This is not an additive interaction since 10 microM of GM1 alone did not significantly modulate TMA-DPH anisotropy. When the GM1 treatment succeeded the addition of toluene the decrease in anisotropy of both probes was reversed. Toluene treatment increased [Ca2+]i in a dose- and time-dependent manner. This increase could partially be both prevented and reversed by treatment with 50 microM of GM1. These effects may reflect an additive interaction, since this concentration of GM1 alone reduced [Ca2+]i. The present results show that toluene increases membrane fluidity and intracellular calcium levels. These effects may be counteracted by the endogenous compound GM1.
von Euler
G
G
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Fuxe
K
K
Bondy
S C
SC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014050:Toluene / Q000494:pharmacology*
D005677:G(M1) Ganglioside; D014050:Toluene; D002118:Calcium