Abstract:
:ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Barg S,Huang P,Eliasson L,Nelson DJ,Obermüller S,Rorsman P,Thévenod F,Renström Ekeywords:
subject
Has Abstractpub_date
2001-06-01 00:00:00pages
2145-54issue
Pt 11eissn
0021-9533issn
1477-9137journal_volume
114pub_type
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