Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology

Abstract

The pancreatic acinar cell is a classical model for studies of secretion and signal transduction mechanisms. Because of the extensive endoplasmic reticulum and the large granular compartment, it has been possible -by direct measurements -to obtain considerable insights into intracellular Ca 2+ handling under both normal and pathological conditions. Recent studies have also revealed important characteristics of stimulus-secretion coupling mechanisms in isolated human pancreatic acinar cells. The acinar cells are potentially dangerous because of the high intra-granular concentration of proteases, which become inappropriately activated in the human disease acute pancreatitis. This disease is due to toxic Ca 2+ signals generated by excessive liberation of Ca 2+ from both the endoplasmic reticulum and the secretory granules.

Endoplasmic Reticulum Stress Is Chronically Activated in Chronic Pancreatitis

“…6B). Our results were consistent with well established pancreatic acinar secretion physiology (31)(32)(33)(34)(35) known to be dependent on transient cytoplasmic Ca 2ϩ changes involving primarily intracellular stores (thus inhibited by BAPTA-AM but not by lack of extracellular Ca 2ϩ ). Further, up-regulation of CHOP (Fig.…”

“…Pathologic calcium signaling is a well studied and well characterized early event in pancreatic injury occurring in response to caerulein hyperstimulation (31)(32)(33)(34)(35). It has previously been shown to mediate pathologic trypsinogen activation and play an important role in NFB activation during early pancreatic injury (28,38,39).…”

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

“…Pancreatic acinar cells play an important role in producing and secreting enzymes for the proper digestion of food. Elevated cytosolic free calcium concentration ([Ca 2+ ] i ) is the critical early signal that triggers the release of digestive enzymes from pancreatic acinar cells [10,11] . Acetylcholine (ACh) and cholecystokinin (CCK) are two typical agonists that activate these intracellular Ca 2+ oscillations, and such agonistinduced Ca 2+ oscillations have been well studied as a classical cellular model of intracellular Ca 2+ signaling [12] .…”

Tench (Tinca tinca) high-throughput transcriptomics reveal feed dependent gut profiles

“…The first two genes, nxpe3 and cplx2, encode proteins essential for trans-synaptic activation and zymogen exocytosis, while the latter also acts as a transmembrane cation transporter and a regulator of membrane potential (Tetreault et al, 2006;Falkowski et al, 2010;Thomas-Jinu and Houart, 2013). The pancreas in fish is highly innervated, with neuronal fibers containing small granular vesicles whose functioning (exocytosis) is triggered by changes in the cytosolic Ca 2 + concentration (Petersen, 2009). Earlier tench studies have shown that the level of feeding and diet composition affect the acinar cells of the pancreas (Krogdahl and Sundby, 1999;Ostaszewska et al, 2006).…”