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AIM To investigate the pharmacological effect of Tong XieYao Fang(TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome(D-IBS) rats.METHODS In a neonatal maternal separation plus restraint stress(NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups(NMS + RS group and TXYF-formula group) with no handlings were used as controls(NH group). Starting from postnatalday 60, rats in TXYF-formula group were administered TXYF-formula(4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator(CFTR) Clchannel, epithelial Na+ channel(ENaC), Ca2+-dependent Cl- channel(CACC), Na+-K+-2Cl- co-transporter(NKCC), and Na+-HCO-3 co-transporter(NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System(AD Instruments International).RESULTS Under basal conditions, the changes of short-circuit current(?Isc, μA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group(70.86 μA/cm2 ± 12.32 μA/cm2, 67.67 μA/cm2 ± 11.68 μA/cm2 vs 38.8 μA/cm2 ± 7.25 μA/cm2, P < 0.01, respectively). When CACC was blocked by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid, 5-HT-induced ?Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively(48.41 μA/cm2 ± 13.15 μA/cm2 vs 74.62 μA/cm2 ± 10.73 μA/cm2, 69.22 μA/cm2 ± 11.7 μA/cm2, P < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride(44.69 μA/cm2 ± 12.58 μA/cm2 vs 62.05 μA/cm2 ± 11.26 μA/cm2, 62.11 μA/cm2 ± 12.01 μA/cm2, P < 0.05, respectively). However, when CFTR Cl- channel was blocked by 1,1-dimethyl piperidinium chloride(DPC), 5-HT-induced ?Isc did not significantly differ in three groups(42.28 μA/cm2 ± 10.61 μA/cm2 vs 51.48 μA/cm2 ± 6.56 μA/cm2 vs 47.75 μA/cm2 ± 7.99 μA/cm2, P > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers.CONCLUSION TXYF-formula can regulate the Cl- and HCO-3 secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO-3 exchanger, NBC and NKCC co-transporters.
AIM To investigate the pharmacological effect of Tong XieYao Fang (TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats. METHODS In a neonatal maternal separation plus restraint stress (NMS + RS) model of D-IBS, male Sprague Dawley rats were divided into two groups (NMS + RS group and TXYF-formula group) with no handlings were used as controls (NH group). Starting from postnatal day 60, rats in TXYF-formula group were administered TXYF-formula (4.92 g / 100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels such as cystic fibrosis transmembrane conductance regulator (CFTR) Clchannel, epithelial Na + channel (ENaC), Ca2 + -dependent Cl- channel (CACC), Na + -K + 3 co-transporter (NBC), in the colonic epithelium of three groups after exposur The results of 5-HT were similar to that of NH group and TXYF- formula group, and both higher than NMS + RS group (70.86 μA / cm2 ± 12.32 μA / cm2, 67.67 μA / cm2 ± 11.68 μA / cm2 vs 38.8 μA / cm2 ± 7.25 μA / cm2, P <0.01 respectively) CACC was blocked by 4,4’-diisothiocyanato-stilbene-2,2’-disulfonic acid, 5-HT-induced? Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively (48.41 μA / cm2 ± 13.15 μA / cm2 vs 74.62 μA / cm2 ± 10.73 μA / cm2, 69.22 μA / cm2 ± 11.7 μA / cm2, P <0.05 respectively) cm2 ± 12.58 μA / cm 2 vs 62.05 μA / cm 2 ± 11.26 μA / cm 2, 62.11 μA / cm 2 ± 12.01 μA / cm 2, P <0.05, respectively). However, when CFTR Cl- chloride (DPC), 5-HT-induced? Isc d id not significantly differ in three groups (42.28 μA / cm2 ± 10.61 μA / cm2 vs 51.48 μA / cm2 ± 6.56 μA / cm2 vs 47.75 μA / cm2 ± 7.99 μA / cm2, P> 0.05, respectively). Similarity could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers. CONCLUSION TXYF-formula can regulate the Cl- and HCO-3 secretion of colonic mucosa via CFTR Cl- channel, Cl- / HCO-3 exchanger, NBC and NKCC co-transporters.