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.