AIM: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 ofTMP on the secretion of pancreatic-bile juice (PBJ) in rats.Using human pancreatic duct cell line,CAPAN-1,combinedwith the short-circuit current (I_(SC)) technique we furtherstudied the effect of TMP on the pancreatic anion secretion.RESULTS:Administration of TMP (80 mg/kg,ip) significantlyincreased the secretion of PBJ (P<0.05),but the pH of PBJand the secretion of pancreatic protein were not significantlyaffected.Basolateral addition of TMP produced a dose-dependent increase in I_(SC) (EC_(50)=1.56 mmol/L),which containeda fast transient Isc response followed by a slow decay.Apicalapplication of Cl~- channel blockers,DPC (1 mmol/L),decreased the response by about 67.1% (P<0.001),whereasamiloride (100 μmol/L),a epithelial sodium channel blockers,had no effect.Removal of extracellular HCO_3~- abolishedTMP-induced increase in I_(SC) by about 74.4% (P<0.001),but the removal of external Cl~- did not.Pretreatment withphosphodiesterase inhibitor,IBMX(0.5 mmol/L),decreasedthe TMP-induced I_(SC) by 91% (P<0.001).CONCLUSION:TMP could stimulate the secretion of PBJ,especially pancreatic ductal HCO_3~- secretion via cAMP orcGMP-dependent pathway.It need further study toinvestigate the roles of cAMP or cGMP in the effect of TMPon the secretion of exocrine pancreas. AIM: 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 (I SC) technique we furtherstudied the effect of TMP on the pancreatic anion secretion. RESULTS: Administration of TMP (80 mg / kg, ip) significantly increased The secretion of PBJ (P <0.05), but the pH of PBJ and the secretion of pancreatic protein were not significantly increased. Basolateral addition of TMP produced a dose-dependent increase in I SCE (EC 50 = 1.56 mmol / L) , which contained a fast transient Isc response followed by a slow decay. A picalapplication of Cl ~ - channel blockers, DPC (1 mmol / L), decreased the response by about 67.1% (P <0.001) a epithelial sodium channel blockers, had no effect. Removal of extracellular HCO 3 ~ - abolished TMP-induce The increase of I SCJ 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 I SCI by 91 % (P <0.001) .CONCLUSION: TMP could stimulate the secretion of PBJ, especially pancreatic ductal HCO 3 - - secretion via cAMP or cGMP-dependent pathway. It needs further study to investigate the roles of cAMP or cGMP in the effect of TMP on the secretion of exocrine pancreas.