Intracellular Ca2+ response of pancreatic acini in cerulein-induced acute pancreatitis in rats.
OBJECTIVE
To approach the mechanism of impaired signal transduction in cerulein-induced pancreatitis, in vitro acinar cell responses including the intracellular Ca2+ dynamics were evaluated.


METHODS
Rats were infused with 10 micrograms/kg/h of cerulein for 4 hours, and the pancreas was dispersed. A binding study for 125I-CCK, intracellular Ca2+ measurement, and an amylase secretion analysis were performed in dispersed pancreatic acini.


RESULTS
The binding study for 125I-CCK revealed that the CCK-binding capacity (Bmax) was decreased, although the binding affinities (Kd high and Kd low) were not altered. An in vitro amylase secretion analysis evoked higher basal secretion but little response. In the control acini, the in vitro application of a physiological dose of CCK (10 pM) evoked intracellular Ca2+ oscillations, and a higher dose of CCK (100 pM, 1 nM) evoked a large transient rise in the intracellular Ca2+ concentration. In cerulein-treated acini, 10 pM CCK evoked no intracellular Ca2+ release, and 100 pM CCK evoked only oscillated Ca2+ concentrations. A higher dose (1 nM) of CCK evoked a transient rise, but the peak Ca2+ level was significantly lower than that in the control (p < 0.05).


CONCLUSIONS
These data suggest that both CCK receptors and intracellular Ca2+ mobilizations are similarly desensitized. The attenuation of amylase secretion is partly due to impaired signal transduction, including impaired intracellular Ca2+ release.
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
N
N
Okada
G
G
Ohshio
T
T
Tanaka
Z H
ZH
Wang
R
R
Doi
M
M
Imamura
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002108:Ceruletide / Q000633:toxicity; D002766:Cholecystokinin / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology
D005765:Gastrointestinal Agents; D011949:Receptors, Cholecystokinin; D002108:Ceruletide; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide; D002118:Calcium