Changes in somatostatin receptor expression of the pancreas and effectiveness of octreotide in rats with acute necrotizing pancreatitis.
OBJECTIVE
To investigate changes in the expression of the somatostatin receptor (SSTR) of the pancreas and of pancreatic blood flow, and its relationship to the metabolism of eicosanoids in order to elucidate the effectiveness of octreotide, an analog of somatostatin, in acute necrotizing pancreatitis (ANP).


METHODS
A model of ANP was induced in rats with injection of sodium taurocholate via the pancreaticobiliary duct. The SSTR was detected using a radioligand binding assay (RBA) with 125I-somatostatin-14, and the SSTR2 mRNA of the pancreas was analyzed using in situ hybridization. Pancreatic blood flow and the metabolites of eicosanoids were also determined.


RESULTS
The SSTR of the pancreas was 109.70 +/- 58.32 fmol/mg protein in normal rats. A significant decrease in the SSTR, together with the signals of SSTR2 mRNA, was shown at 3, 6 and 12 h after onset of ANP. Pancreatic blood flow was reduced and thromboxin-2 was increased significantly in the course of ANP. In the ANP group treated with octreotide, both the decrease in pancreatic blood flow and the abnormal metabolism of eicosanoids were corrected, and the pathological damage was relieved.


CONCLUSIONS
SSTR expression of the pancreas is significantly reduced in ANP. Correction of the abnormal metabolism of eicosanoids and improvement in pancreatic microcirculation may be the major mechanism of somatostatin analogs in the treatment of ANP and inhibition of pancreatic enzymes via their receptors plays a minor role.
Wu
Jian Xin
JX
Department of Gastroenterology, Xinhua Hospital, Shanghai Second Medical University, Shanghai, China. wjxgp@public9.sta.net.cn
Yuan
Yao Zong
YZ
Xu
Jia Yu
JY
Xia
Zong Qin
ZQ
Qin
Lan Feng
LF
Zheng
Zheng Lin
ZL
Li
Ding Guo
DG
Lu
Han Ming
HM
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D015232:Dinoprostone / Q000097:blood; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D010179:Pancreas / Q000098:blood supply / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood
D005765:Gastrointestinal Agents; D017481:Receptors, Somatostatin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D015282:Octreotide