Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion.

Abstract

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