期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 40, 页码 14386-14391出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503215102
关键词
acinar cell; dantrolene; calcium signaling
资金
- FIC NIH HHS [TW01451, R03 TW001451] Funding Source: Medline
- NICHD NIH HHS [K12 HD001401] Funding Source: Medline
- NIDDK NIH HHS [KO8 DK68116, T32 DK007017, DK34989, DK45710, DK54021, R01 DK045710, K08 DK068116, T32 DK07017, P30 DK034989, R01 DK054021] Funding Source: Medline
Acute pancreatitis is characterized by the pathologic activation of zymogens within pancreatic acinar cells. The process requires a rise in cytosolic Ca2+ from undefined intracellular stores. We hypothesized that zymogen activation is mediated by ryanodine receptor (RYR)-regulated Ca2+ release, because early zymogen activation takes place in a supranuclear compartment that overlaps-in distribution with the RYR. Ca2+ signals in the basolateral, but not apical, region of acinar cells observed during supraphysiologic agonist stimulation were dependent on RYR Ca2+ release. Inhibition of RYR or depletion of RYR-sensitive Ca2+ pools each reduced pathologic zymogen activation in isolated acinar cells, but neither treatment affected amylase secretion. Inhibition of RYR also inhibited zymogen activation in vivo. We propose that Ca2+ release from the RYR mediates zymogen activation but not enzyme secretion. The findings imply a role for the RYR in acute pancreatitis.
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