Basic—Liver, Pancreas, and Biliary TractDirect Activation of Cytosolic Ca2+ Signaling and Enzyme Secretion by Cholecystokinin in Human Pancreatic Acinar Cells⁎,
Section snippets
Collection of Human Pancreatic Samples
The study was approved by the Liverpool Adult Local Research Ethics Committee (Reference: 03/12/242/A) and written informed consent for sampling was obtained from all patients before surgery. Sampling for these experiments was restricted to patients undergoing surgery for left-sided or small unobstructing pancreatic tumors in otherwise normal pancreata, because preliminary experiments showed that samples from patients with ductal obstruction (eg, from pancreatic cancer) or chronic pancreatitis
Characteristics of Patients, Pancreatic Samples, and Acinar Cell Isolates
Pancreatic samples were donated by 14 patients (mean age, 59 y; range, 25–82 y) undergoing surgery between November 2005 and February 2008 (Table 1). Histopathologic examination of the excised specimen at the pancreatic transection line confirmed normal pancreatic histology in every case, but for mild fibrosis in 4. Isolated acinar cells typically showed excellent morphology, with strong polarity delineated by a distinct granular region in the apical pole of each cell, and no intracellular
Discussion
Our data show that 2 different forms of CCK, CCK-8 and human CCK-58, activate human pancreatic acinar cells at a range of CCK concentrations normally expected in vivo,13 generating robust and reversible intracellular Ca2+ signals that are followed by stimulation of mitochondrial metabolism and exocytosis of digestive enzymes, shown here in real time. Pancreatic enzyme secretion occurs by exocytosis and it is well established in general, as in the pancreas, that exocytosis is initiated by an
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2022, Molecular TherapyCitation Excerpt :Small (<1 cm2 × 1 mm) samples of viable pancreas were taken from patients undergoing surgery for symptomatic pseudocysts complicating AP or for infected pancreatic necrosis. Normal pancreatic samples (<1 cm2 × 1 mm) were taken from patients undergoing surgery for left-sided or small unobstructing pancreatic tumors following Liverpool's protocols.44 C57BL/6 background, 10- to 12-week-old, male WT or genetically modified mice were used throughout the study.
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J.A.M. and D.N.C. contributed equally to this work.
This work was supported by Programme, Cooperative, and Component grants from the Medical Research Council (UK), and by National Institutes of Health grants DK 33850 (J.R.R.), and DK 37482 (G.M.G.), by the Veterans Administration Research Service, and by the National Institutes of Health CURE: Digestive Diseases Research Center grant DK41301. O.H.P. is a Medical Research Council Professor; J.M. was, and R.M. is, supported by an Amelie Waring Clinical Research Fellowship from CORE; and E.M. is supported by a Clinical Training Fellowship from the Royal College of Surgeons of England.