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.
Morgan
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Physiological Laboratory, University of Liverpool, UK.
Burgoyne
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D020727:ADP-Ribosylation Factors; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects / Q000378:metabolism*; D004072:Digitonin / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*
D002395:Catecholamines; D010446:Peptide Fragments; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; D004072:Digitonin; D002118:Calcium