Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion

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 (ISC) technique we further studied 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 affected. Basolateral addition of TMP produced a dosedependent 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 μmol/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, TBMX(0.5 mmol/L), decreased the TMP-induced ISC by 91% (P<0.001).CONCLUSION: TMP could stimulate the secretion of PBJ,especially pancreatic ductal HCO3- secretion via cAvlp 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.

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 further studied 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 affected.Basolateral addition of TMP produced a dose- dependent increase in I_(SC) (EC_(50)=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 μmol/L),a epithelial sodium channel blockers, had no effect.Removal of extracellular HCO_3^- abolished TMP-induced increase in I_(SC) 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_(SC) 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 need further study to investigate the roles of cAMP or cGMP in the effect of TMP on the secretion of exocrine pancreas.