Intervention of pyrrolidine dithiocarbamate and tetrandrine on cellular calcium overload of pancreatic acinar cells induced by serum and ascitic fluid from rats with acute pancreatitis.
OBJECTIVE
To investigate the effects of serum and ascitic fluid from rats with acute pancreatitis (AP) on cellular free calcium concentration ([Ca(2+)]i) of isolated rat pancreatic acinar cells, and the intervention of pyrrolidine dithiocarbamate (PDTC) and tetrandrine (Tet) to cellular calcium overload in AP.


METHODS
AP was induced in Sprague-Dawley rats with a retrograde pancreatic duct injection of 3% sodium deoxycholate, and confirmed by histopathological examination and amylase activity assay. The rat serum and ascitic fluid were collected at 1, 5 and 10 h after AP induction, and used as irritants on isolated rat pancreatic acinar cells. The effects on intracellular [Ca(2+)]i, and cell viability were examined. Then, the antagonistic effects of different concentrations of PDTC and Tet were assessed.


RESULTS
The irritation with AP serum and ascitic fluid reduced the survival rate of the isolated rat pancreatic acinar cells and increased the cellular [Ca(2+)]i significantly (P < 0.05). As AP induction course prolonged, the stimulation effect of the AP serum and ascitic fluid intensified. In the pretreated acinar cells with PDTC or Tet, the decreased cell vitality reverted. The elevation of [Ca(2+)]i in the acinar cells significantly ameliorated (significant, P < 0.05; very significant, P < 0.01).


CONCLUSIONS
The serum and ascitic fluid from AP rats drastically elevate the [Ca(2+)]i in isolated pancreatic acinar cells and decrease cell vitality, while the pretreatment of cells with PDTC and Tet offsets the calcium overload irritated by the AP serum and ascitic fluid and protects these isolated acinar cells.
Li
Yong-Yu
YY
Department of Pathophysiology, Institute of Digestive Disease, Medical School of Tongji University, Shanghai, China. liyongyu@mail.tongji.edu.cn
Lu
Xin-Yuan
XY
Li
Xue-Jin
XJ
Li
Yan-Na
YN
Li
Kun
K
Chen
Chang-Jie
CJ
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001202:Ascitic Fluid / Q000378:metabolism*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003840:Deoxycholic Acid; D004195:Disease Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D003840:Deoxycholic Acid; C020972:pyrrolidine dithiocarbamic acid; C009438:tetrandrine; D000681:Amylases; D002118:Calcium