Effect of tetramethyplyrazine on exocrine pancreatic and bile secretion

摘要

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 I_(SC) response followed by a slow decay. Apical application of CI~- 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% 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.