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. 2016 Dec 28;22(48):10584-10591.
doi: 10.3748/wjg.v22.i48.10584.

Regulating effect of TongXie-YaoFang on colonic epithelial secretion via Cl- and HCO3- channel

Cheng Yang  1 , Ying Xiong  1 , Sheng-Sheng Zhang  1 , Fang-Mei An  1 , Jing Sun  1 , Qing-Lin Zhang  1 , Qiang Zhan  1
Affiliations

Regulating effect of TongXie-YaoFang on colonic epithelial secretion via Cl- and HCO3- channel

Cheng Yang et al. World J Gastroenterol. .

Abstract

Aim: To investigate the pharmacological effect of TongXie-YaoFang (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 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) Cl- channel, epithelial Na+ channel (ENaC), Ca2+-dependent Cl- channel (CACC), Na+-K+-2Cl- co-transporter (NKCC), and Na+-HCO3- 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/cm2vs 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/cm2vs 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/cm2vs 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/cm2vs 51.48 µA/cm2 ± 6.56 µA/cm2vs 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 HCO3- secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO3- exchanger, NBC and NKCC co-transporters.

Keywords: Colonic mucosa; Diarrhea-predominant irritable bowel syndrome; Ion channel; Short-circuit current; TongXie-YaoFang formula.

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Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Figures

Figure 1
Figure 1
Comparison of basic electrophysiological properties of colonic mucosa in rats and 5-HT-induced the changes of short-circuit current among three groups. A-C: The basic Isc, basic voltage and basic resistance did not differ significantly between three groups, respectively (P > 0.05, respectively); D: TXYF-formula significantly increased 5-HT-induced ∆Isc in neonatal maternal separation plus restraint stress (NMS + RS) rats. bP < 0.01 vs NMS + RS group. Isc: The short-circuit current; ∆Isc: The changes of Isc; TXYF: TongXie-YaoFang; NMS: Neonatal maternal separation; RS: Restraint stress; NH: No handlings as control.
Figure 2
Figure 2
Effects of 1,1-dimethyl piperidinium chloride, Glibenclamide, cystic fibrosis transmembrane conductance regulator(inh)-172, 4,4’-diisothiocyanato-stilbene-2,2’-disulfonic acid, Amiloride and Bumetanide on 5-HT-induced the changes of short-circuit current in rats. A: After the intervention with DPC, Glibenclamide or CFTR(inh)-172, respectively, ∆Isc induced by 5-HT were similar in three groups (P > 0.05, respectively); B: 5-HT-induced ∆Isc was higher in TXYF-formula group than in NMS + RS group after the intervention with DIDS or Amiloride. aP < 0.05 vs NMS + RS group; bP < 0.01 vs NMS + RS group. DPC: 1,1-dimethyl piperidinium chloride; CFTR: Cystic fibrosis transmembrane conductance regulator; ∆Isc: the changes short-circuit current; DIDS: 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid; TXYF: TongXie-YaoFang; NMS: Neonatal maternal separation; RS: Restraint stress; NH: No handlings as control.
Figure 3
Figure 3
Effects of BaCl2, 4-acetamido-4’-isothio-cyanato-stilbene-2,2’-disulfonic and 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid on 5-HT-induced the changes of short-circuit current in rats. 5-HT-induced ∆Isc were similar in three groups after the intervention with BaCl2, SITS or DIDS, respectively (P > 0.05, respectively). ∆Isc: the changes short-circuit current; SITS: 4-acetamido-4′-isothio-cyanato-stilbene-2,2′-disulfonic; DIDS: 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid; TXYF: TongXie-YaoFang; NMS: Neonatal maternal separation; RS: Restraint stress; NH: No handlings as control.
Figure 4
Figure 4
Effects of Na+, Cl– and HCO3– on 5-HT-induced the changes of short-circuit current in rats. A: 5-HT-induced ∆Isc was higher in TXYF-formula group than in NMS + RS group when Na+ in apical side of colonic mucosa was taken out; B: When Na+ in basolateral side was taken out, ∆Isc was similar in three groups; C: 5-HT-induced ∆Isc was similar in three groups when Cl– and HCO3– was respectively or entirely removed from basolateral side of colonic mucosa. aP < 0.05 vs NMS + RS group; bP < 0.01 vs NMS + RS group. ∆Isc: the changes short-circuit current; TXYF: TongXie-YaoFang; NMS: Neonatal maternal separation; RS: Restraint stress; NH: No handlings as control.
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