IP3 receptor type 2 deficiency is associated with a secretory defect in the pancreatic acinar cell and an accumulation of zymogen granules.

Autor: Abrahim I Orabi, Yuhuan Luo, Mahwish U Ahmad, Ahsan U Shah, Zahir Mannan, Dong Wang, Sheharyar Sarwar, Kamaldeen A Muili, Christine Shugrue, Thomas R Kolodecik, Vijay P Singh, Mark E Lowe, Edwin Thrower, Ju Chen, Sohail Z Husain
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 11, p e48465 (2012)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0048465
Popis: Acute pancreatitis is a painful, life-threatening disorder of the pancreas whose etiology is often multi-factorial. It is of great importance to understand the interplay between factors that predispose patients to develop the disease. One such factor is an excessive elevation in pancreatic acinar cell Ca(2+). These aberrant Ca(2+) elevations are triggered by release of Ca(2+) from apical Ca(2+) pools that are gated by the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3. In this study, we examined the role of IP3R type 2 (IP3R2) using mice deficient in this Ca(2+) release channel (IP3R2(-/-)). Using live acinar cell Ca(2+) imaging we found that loss of IP3R2 reduced the amplitude of the apical Ca(2+) signal and caused a delay in its initiation. This was associated with a reduction in carbachol-stimulated amylase release and an accumulation of zymogen granules (ZGs). Specifically, there was a 2-fold increase in the number of ZGs (P
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