ADP-RIBOSYLATION OF RHO-PROTEINS IS INHIBITED BY MELITTIN, MAST-CELL DEGRANULATING PEPTIDE AND COMPOUND-48/80

The amphiphilic agents melittin, mast cell degranulating peptide and compound 48/80 inhibit the ADP-ribosylation of the small GTP-binding proteins rho by Clostridium botulinum exoenzyme C3. Half-maximal and maximal inhibition (> 90%) of ADP-ribosylation occurred at about 8 and 25-mu-g/ml for compound 48/80, at 10 and 45-mu-M for mast cell degranulating peptide and at 15 and 50-mu-M for melittin, respectively. In addition, these compounds increase the steady state GTP hydrolysis and the association and dissociation rate of GTP-binding of rho proteins through an increase of GDP/GTP exchange. The data suggest that the amphiphilic agents tested interact with small GTP-binding proteins of the rho protein family.