Role of vesicular nucleotide transporter VNUT (SLC17A9) in release of ATP from AR42J cells and mouse pancreatic acinar cells.
ATP is released from cells in response to various stimuli. Our previous studies on pancreas indicated that pancreatic acini could be major stores of secreted ATP. In the present study, our aim was to establish the role of the vesicular nucleotide transporter (VNUT), SLC17A9, in storage and release of ATP. Freshly prepared acini from mice and AR42J rat acinar cells were used in this study. We illustrate that in AR42J cells, quinacrine (an ATP store marker) and Bodipy ATP (a fluorescent ATP analog) co-localized with VNUT-mCherry to vesicles/granules. Furthermore, in acini and AR42J cells, a marker of the zymogen granule membranes, Rab3D, and VNUT co-localized. Dexamethasone treatment of AR42J cells promoted formation of acinar structures, paralleled by increased amylase and VNUT expression, and increased ATP release in response to cholinergic stimulation. Mechanical stimulus (pressure) and cell swelling also induced ATP release, but this was not influenced by dexamethasone, most likely indicating different non-zymogen-related release mechanism. In conclusion, we propose that VNUT-dependent ATP release pathway is associated with agonist-induced secretion process and downstream purinergic signalling in pancreatic ducts.
Department of Biology, Section Molecular Integrative Physiology, University of Copenhagen, August Krogh Building, Universitetsparken 13, Copenhagen, 2100, Denmark.
K A
KA
Haanes
J M
JM
Kowal
G
G
Arpino
S C
SC
Lange
Y
Y
Moriyama
P A
PA
Pedersen
I
I
Novak
D061354:Acinar Cells / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D033704:Nucleotide Transport Proteins / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism*; D051381:Rats
D033704:Nucleotide Transport Proteins; C578984:Slc17a9 protein, mouse; D000255:Adenosine Triphosphate