Relationship between carbachol hyperstimulation-induced pancreatic acinar cellular injury and trypsinogen or NF-kappaB activation in rats in vitro.
The relationship between M3 cholinergic receptor agonist (carbachol) hyperstimulation-induced pancreatic acinar cellular injury and trypsinogen activation or NF-kappaB activation in rats was studied in vitro. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc), and NF-kappaB inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The cellular injury was evaluated by measuring the leakage of LDH from pancreatic acinar cells. The results showed that as compared with control group, 10(-3) mol/L carbachol induced a significant increase of the intracellular trypsin activity and the leakage of LDH from pancreatic acinar cells. Pretreatment with 2 mmol/L pefabloc could significantly decrease the activity of trypsin and the leakage of LDH from pancreatic acinar cells (P < 0.01) following the treatment with a high concentration of carbachol (10(-3) mol/L) in vitro. The addition of 10(-2) mol/L PDTC didn't result in a significant decrease in the activity of trypsin and the leakage of LDH from pancreatic acinar cells treated with a high concentration of carbachol (10(-3) mol/L) in vitro (P > 0.05). It was concluded that intracellular trypsinogen activation is likely involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro. NF-kappaB activation may not be involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro.
Hai
Zheng
Z
Department of Emergency Surgery, Union Hospital, Tonji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Jiang
Chunfang
C
Zhang
Jinxiang
J
Wang
Linfang
L
Fang
Kaifeng
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000819:agonists; D014362:Trypsinogen / Q000378:metabolism*
D018679:Cholinergic Agonists; D016328:NF-kappa B; D043587:Receptor, Muscarinic M3; D002217:Carbachol; D014362:Trypsinogen