Islet cell-activating protein reverses anti-fucosyl GM1 ganglioside antibody-induced inhibition of adenosine 3',5'-monophosphate production in FRTL-5 rat thyroid cells

Our previous study revealed that a specific antibody against fucosyl GM1 ganglioside (fGM1) inhibits basal and ligand-stimulated cAMP production in FRTL-5 rat thyroid cells. To further elucidate the mechanism of this inhibitory action of the antibody, the involvement of guanine nucleotide-binding proteins was studied using islet cell-activating protein (IAP) and cholera toxin. When FRTL-5 cells were pretreated with IAP and incubated with the antibody, the inhibitory activity of the antibody on cAMP production was completely abolished. Furthermore, the inhibitory activity of the antibody on TSH- or forskolin-stimulated cAMP production was also abolished by IAP preincubation. The inhibitory activity of the antibody by pretreatment of the cells was also reversed by the addition of IAP. Coincubation of FRTL-5 cells with the antibody and cholera toxin reduced the cAMP inhibitory action of the antibody. Similar results were obtained with anti-fGM1 pretreatment before cholera toxin stimulation. These results provide evidence that anti-fGM1 antibody acts via guanine nucleotide-binding proteins in inhibiting cAMP production in FRTL-5 cells.