A role for anion transport in the regulation of release from chromaffin granules and exocytosis from cells

Release of epinephrine from isolated adrenergic secretory vesicles from the adrenal medulla (chromaffin granules) was found to be inhibited by a number of anion transport blocking agents, including SITS, probenecid, pyridoxal phosphate, and Na-isethionate. High concentrations of permeant anion, such as chloride, are required for granule release and the drugs were found to be competitive inhibitors with respect to chloride. The anion transport blockers were also found to suppress exocytosis of serotonin from human platelets and parathyroid hormone from dissociated bovine parathyroid cells. By contrast, they had no effect on ACTH-activated corticosterone secretion from dissociated rat adrenocortical cells, a process which occurs by diffusion rather than exocytosis. The important anion in the medium for human platelets was hydroxyl ion, rather than chloride, and the most effective drug on platelets was suramin. Isethionate was inactive. In the case of PTH secretion, both chloride and hydroxyl ions were important anions and were both competitively inhibited by anion blocking drugs including Na-isethionate. The authors conclude from these studies that the chemistry of exocytosis appears to be quite similar to the chemistry of release from isolated secretory vesicles. The authors suggest that when vesicles are fused to plasma membranes prior to exocytosis they are exposed to higher chloride and hydroxyl ion concentrations of the medium, and that inward anion flux into the vesicle promotes release, possibly by local osmotic lysis. Blockade of exocytosis by anion transport blocking drugs would occur by inhibition of inward anion flux into the fused vesicle, by analogy with previous results from studies on isolated chromaffin granules.