Intracellular Ca2+ dynamics and in vitro secretory response in acute pancreatitis induced by a choline-deficient, ethionine-supplemented diet in mice.
In order to approach impaired stimulus-secretion coupling in acute pancreatitis induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the agonist-evoked intracellular Ca2+ dynamics of dispersed pancreatic acini were evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h, and the pancreas was dispersed to the acini. The in vitro amylase secretion analysis of the CDE groups demonstrated a poor dose-response curve which was significantly lower (p < 0.01) when 100 pM cholecystokinin (CCK) was administered. Both in CDE and control groups, the application of a physiological dose of CCK-8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and amplitude of the oscillations in the CDE groups were not significantly different. The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and transient rise in intracellular Ca2+, followed by a small, continuous increase above basal levels for the duration of stimulation both in CDE and control groups. The peak Ca2+ level was lower in the CDE groups, but this was not statistically significant. In conclusion, during the early phase (from 24 to 48 h) of CDE pancreatitis, the pattern of agonist-evoked intracellular Ca2+ release is less affected. Other mechanisms subsequent to the onset of intracellular Ca2+ release are likely to be involved in the inhibition of enzyme secretion.
1st Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
N
N
Okada
G
G
Ohshio
T
T
Manabe
M
M
Imamura
Y
Y
Habara
T
T
Kanno
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002796:Choline Deficiency / Q000150:complications*; D005001:Ethionine / Q000008:administration & dosage*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012844:Sincalide / Q000494:pharmacology
D000681:Amylases; D012844:Sincalide; D002118:Calcium; D005001:Ethionine