2005 Volume 55 Issue 6 Pages 325-329
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 (Isc) 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 Isc, 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 Isc 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 Isc. (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 Isc, 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 Isc 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 Isc 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.