The Underlying Cellular Mechanism in the Effect of Tetramethylpyrazine on the Anion Secretion of Colonic Mucosa

Abstract

The present study investigated the underlying cellular mechanism in the effect of ligustrazine (tetramethylpyrazine, TMP) on the anion secretion of colonic mucosa in rats using a short-circuit current (I_sc) technique in conjunction with “tool drugs.” (i) After a pretreatment of the tissues by bathing the bilateral surface with Cl⁻-free Krebs-Henseleit (K-H) solution for over an hour, a basolateral application of 1 mmol/l TMP produced an increase in I_sc, and the total charges transported for 30 min were about 8.7 ± 1.4 mC/cm²; an apical pretreatment of DPC and a basolateral addition of acetazolamide decreased the TMP-induced I_sc by about 60% (P < 0.01) and 45% (P < 0.05), respectively; a basolateral application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), the inhibitor of Na⁺-HCO₃⁻ cotransporter (NBC), did not alter the TMP-induced I_sc. (ii) After the bilateral surface of mucosa was bathed with HCO₃⁻-free K-H solution for over an hour, a basolateral application of 1 mmol/l TMP produced an increase in I_sc, and the total charges transported in 30 min were about 8.3 ± 1.9 mC/cm²; an apical pretreatment of DPC (1 mmol/l), the inhibitor of Cl⁻ channels, decreased the TMP-induced I_sc by about 84% (P < 0.01). The basolateral presence of bumetanide (0.1 mmol/l), the inhibitor of Na⁺-K⁺-Cl⁻ cotransporter (NKCC), significantly reduced the TMP-evoked I_sc by about 86% (P < 0.01). In conclusion, (i) ligustrazine could promote colonic mucosa secretion Cl⁻ via apical Cl⁻ channels and basolateral NKCC; (ii) ligustrazine could promote colonic mucosa secretion HCO₃⁻ via apical Cl⁻ channels and the basolateral diffusion of CO₂.