BREFELDIN-A AND A SYNTHETIC PEPTIDE TO ADP-RIBOSYLATION FACTOR (ARF) INHIBIT REGULATED EXOCYTOSIS IN MELANOTROPHS

WE investigated the role of ADP-ribosylation factor (ARF) in regulated exocytosis in patch-clamped rat melanotrophs. Addition of brefeldin A (BFA) to inhibit activation of endogenous ARF protein was found to attenuate regulated secretory activity monitored as changes in membrane capacitance (C-m). A synthetic peptide to amino acids 46-61 of ARF (P-14) was also found to inhibit Ca2+-induced secretory activity in these cells. This inhibition was not apparent with a scrambled amino acid sequence of ARF-P14 peptide. This paper provides the first patch-clamp study to suggest that the small GTP-binding protein ARF is required to trigger release of secretory granules from rat pituitary melanotrophs.