[Effects of analogs of pituitary adenylate cyclase activating polypeptide on acute pancreatitis in rats].
OBJECTIVE
To examine the effects of analogs of pituitary adenylate cyclase activating polypeptide (PACAP)--PACAP6-27 (10, 100 microg/kg) and (4-Cl-D-Phe6, Leu17)VIP (10, 100 microg/kg) on the pancreata of normal rats and on the development of experimental acute pancreatitis.


METHODS
Male Wistar rats were allocated into normal control groups, experimental acute pancreatitis groups and PACAP analog intervention groups. Acute pancreatitis was induced with s.c. cerulein and intraductal sodium taurocholate; PACAP analogs were infused intravenously immediately after pancreatitis induction. Pancreatic morphology was observed at 4 h, and serum amylase, pancreatic water content and PACAP contents were measured.


RESULTS
It was found that PACAP6-27 induced pancreatic edema, inflammatory cell infiltration, and elevation of serum amylase [(1464.33 +/- 265.6)-(1692.17 +/- 312.18)] IU/L vs (520.8 +/- 163.27) IU/L of control, P < 0.05); that PACAP6-27 aggravated vacuolization of pancreatic acinar cells in cerulein-induced pancreatitis with hemorrhage and fatty and parenchymal necrosis; and that the pathological changes of cerulein plus 100 microg/kg PACAP group were similar to those of sodium taurocholate-induced pancreatitis. Pancreatic hemorrhage, vacuolization of acinar cells and parenchymal necrosis in sodium taurocholate-induced pancreatitis were worsened by PACAP6-27. (4-Cl-D-Phe6, Leu17)VIP had similar effects. ELISA showed that pancreatic and duodenal levels of PACAP were increased in cerulein- and sodium taurocholate-induced pancreatitis.


CONCLUSIONS
PACAP6-27 and (4-Cl-D-Phe6, Leu17)VIP could induce mild pancreatitis and aggravate experimental acute pancreatitis. PACAP probably plays a role in the pathogenesis of acute pancreatitis.
Chen
You-dai
YD
Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhou
Zong-guang
ZG
Yan
Wen-wei
WW
Wang
Zhao
Z
Gao
Hong-kai
HK
Zheng
Xue-lian
XL
D000208:Acute Disease; D000818:Animals; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D009479:Neuropeptides / Q000037:antagonists & inhibitors*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors
C495403:Adcyap1 protein, rat; D006727:Hormone Antagonists; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; C106317:pituitary adenylate-cyclase-activating peptide (6-27)