EFFECT OF GANGLIOSIDE GM1 ON ARACHIDONIC-ACID RELEASE IN BOVINE AORTIC ENDOTHELIAL-CELLS

A role for the ganglioside GM1 in arachidonic acid release in bovine a ortic endothelial cells (BAEC) was investigated. [H-3]Arachidonic acid -labeled BAEC were preincubated with GM1 and incubated with one of fou r different stimulators. GM1 inhibited arachidonic acid release when s timulated with maitotoxin or melittin but not with ionomycin or thapsi gargin. A 10 muM GM1 concentration achieved a 50% and 100% inhibition of the maitotoxin and melittin responses, respectively. The selective inhibition displayed by GM1 on the maitotoxin and melittin responses w as not due to its ability to bind calcium since all four drugs, maitot oxin, melittin, ionomycin, and thapsigargin, required extracellular ca lcium. The effect of GM1 was not specific to arachidonic acid release. GM1 at 50 muM inhibited phosphatidyl-inositol polyphosphate (PIP) hyd rolysis mediated by melittin, but did not affect hydrolysis mediated b y ionomycin. Moreover, the activity of GM1 was not restricted to phosp holipid metabolism since it also inhibited calcium influx that was sti mulated by maitotoxin or melittin but not by ionomycin. We conclude th at GM1 is not a specific inhibitor of phospholipases in bovine aortic endothelial cells, but rather its activity is dependent on the type of stimulant used to activate the cell.