Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion.
OBJECTIVE
To investigate the effect of tetramethylpyrazine (ligustrazine, TMP) on the secretion of exocrine pancreas (and biliary).


METHODS
In in vivo study, we investigated the effect of TMP on the secretion of pancreatic-bile juice (PBJ) in rats. Using human pancreatic duct cell line, CAPAN-1, combined with the short-circuit current (ISC) technique we further studied the effect of TMP on the pancreatic anion secretion.


RESULTS
Administration of TMP (80 mg/kg, i.p.) significantly increased the secretion of PBJ (P<0.05), but the pH of PBJ and the secretion of pancreatic protein were not significantly affected. Basolateral addition of TMP produced a dose-dependent increase in ISC (EC50=1.56 mmol/L), which contained a fast transient ISC response followed by a slow decay. Apical application of Cl- channel blockers, DPC (1 mmol/L), decreased the response by about 67.1% (P<0.001), whereas amiloride (100 micromol/L), a epithelial sodium channel blockers, had no effect. Removal of extracellular HCO3- abolished TMP-induced increase in ISC by about 74.4% (P<0.001), but the removal of external Cl- did not. Pretreatment with phosphodiesterase inhibitor, IBMX(0.5 mmol/L), decreased the TMP-induced ISC by 91% (P<0.001).


CONCLUSIONS
TMP could stimulate the secretion of PBJ, especially pancreatic ductal HCO3- secretion via cAMP or cGMP-dependent pathway. It need further study to investigate the roles of cAMP or cGMP in the effect of TMP on the secretion of exocrine pancreas.
Zhao
Wen-Chao
WC
Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, SAR, China.
Zhu
Jin-Xia
JX
Tang
Ning
N
Gou
Yu-Lin
YL
Rowlands
Dewi Kenneth
DK
Chung
Yiu-Wa
YW
Xing
Ying
Y
Chan
Hsiao-Chang
HC
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008297:Male; D010179:Pancreas / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; C017953:tetramethylpyrazine