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Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells

Voronina, S. G., Barrow, S. L., Simpson, A. W. M., Gerasimenko, Oleg Vsevolodovich, Xavier, G. D. S, Rutter, G. A., Petersen, Ole Holger and Tepikin, A. V. 2010. Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells. Gastroenterology 138 (5) , pp. 1976-1987. 10.1053/j.gastro.2010.01.037

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Abstract

Background & Aims Previous studies of pancreatic acinar cells characterized the effects of Ca2+-releasing secretagogues and substances, inducing acute pancreatitis on mitochondrial Ca2+, transmembrane potential, and NAD(P)H, but dynamic measurements of the crucial intracellular adenosine triphosphate (ATP) levels have not been reported. Here we characterized the effects of these agents on ATP levels in the cytosol and mitochondria. Methods ATP levels were monitored using cytosolic- or mitochondrial-targeted luciferases. Results Inhibition of oxidative phosphorylation produced a substantial decrease in cytosolic ATP comparable to that induced by inhibition of glycolysis. Cholecystokinin-8 (CCK) increased cytosolic ATP in spite of accelerating ATP consumption. Acetylcholine, caerulein, and bombesin had similar effect. A bile acid, taurolithocholic acid 3-sulfate (TLC-S); a fatty acid, palmitoleic acid (POA); and palmitoleic acid ethyl ester (POAEE) reduced cytosolic ATP. The ATP decrease in response to these substances was observed in cells with intact or inhibited oxidative phosphorylation. TLC-S, POA, and POAEE reduced mitochondrial ATP, whereas physiological CCK increased mitochondrial ATP. Supramaximal CCK produced a biphasic response composed of a small initial decline followed by a stronger increase. Conclusions Both glycolysis and oxidative phosphorylation make substantial contributions to ATP production in acinar cells. Ca2+-releasing secretagogues increased ATP level in the cytosol and mitochondria of intact isolated cells. TLC-S, POA, and POAEE reduced cytosolic and mitochondrial ATP. When cells rely on nonoxidative ATP production, secretagogues as well as TLC-S, POA, and POAEE all diminish cytosolic ATP levels.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QM Human anatomy
Q Science > QP Physiology
Uncontrolled Keywords: Pancreas; ATP; Ca2+ Signaling; Pancreatitis; Bile Acids; Luciferase; CCK
Publisher: Elsevier
ISSN: 0016-5085
Last Modified: 04 Jun 2017 02:05
URI: http://orca-mwe.cf.ac.uk/id/eprint/8891

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