A synthetic peptide of the N-terminus of ADP-ribosylation factor (ARF) inhibits regulated exocytosis in adrenal chromaffin cells.

We have investigated the role of ADP-ribosylation factor (ARF) in regulated exocytosis in digitonin-permeabilized adrenal chromaffin cells by the use of a synthetic peptide, hARF1(2-17), based on the N-terminus of the protein. hARF1(2-17) inhibited Ca(2+)-dependent but not basal exocytosis, whereas equimolar levels of other synthetic peptides were ineffective. The inhibitory effect of hARF1(2-17) was dose-dependent and half-maximal at 12 microM. GTP gamma S-induced secretion in the presence of non-stimulatory CA2+ concentrations was also inhibited by hARF1(2-17). These results point to a hitherto unsuspected role for ARF in regulated exocytosis, and the potency of the hARF1(2-17) peptide suggests that ARF is essential for exocytosis in bovine adrenal chromaffin cells.