ACTIVATION OF EXOCYTOSIS BY GTP ANALOGS IN ADRENAL CHROMAFFIN CELLS REVEALED BY PATCH-CLAMP CAPACITANCE MEASUREMENT

The role of GTP-binding proteins in exocytosis in bovine adrenal chromaffin cells was examined using patch-clamp capacitance measurement. Internal dialysis with the non-hydrolysable GTP analogue guanosine 5'-[beta gamma-imido]triphosphate and xanthosine triphosphate (XTP) activated a capacitance increase. Exocytosis triggered by XTP was blocked by guanosine 5'-[beta-thio]diphosphate (GDP beta S) but Ca2+-induced exocytosis was unaffected. The capacitance increase due to XTP could not be explained by Ca2+ mobilisation since Ins(1,4,5)P-3 and caffeine did not mimic the response. Chromaffin cells appear to possess a Ca2+-independent pathway for exocytosis that involves GTP-binding proteins. The magnitude of the response to XTP suggested that GTP analogues stimulate both exocytosis and recruitment of secretory granules.