title: Regulating effect of TongXie-YaoFang on colonic epithelial secretionviaCl-and HCO3-channel.
abstract: OBJECTIVE
  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/cm2vs38.8 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/cm2vs74.62 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/cm2vs62.05 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/cm2vs51.48 µA/cm2± 6.56 µA/cm2vs47.75 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.
  
  
  CONCLUSIONS
  TXYF-formula can regulate the Cl-and HCO3-secretion of colonic mucosaviaCFTR Cl-channel, Cl-/HCO3-exchanger, NBC and NKCC co-transporters.
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Sheng-Sheng
authors.initials: SS
authors.lastname: Zhang
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Fang-Mei
authors.initials: FM
authors.lastname: An
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Qing-Lin
authors.initials: QL
authors.lastname: Zhang
authors.affiliation: Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects*; D003106:Colon / Q000378:metabolism; D003967:Diarrhea / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D010880:Piperidines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D027982:Sodium-Bicarbonate Symporters / Q000037:antagonists & inhibitors / Q000187:drug effects*; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications; D055815:Young Adult
chemical_list: D018118:Chloride Channels; D004365:Drugs, Chinese Herbal; D062686:Epithelial Sodium Channel Blockers; D010880:Piperidines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D027982:Sodium-Bicarbonate Symporters; D028021:Sodium-Potassium-Chloride Symporters; C000601593:tongxie-yaofang; D000584:Amiloride; D006916:5-Hydroxytryptophan; C049449:mepiquat
keywords: Colonic mucosa; Diarrhea-predominant irritable bowel syndrome; Ion channel; Short-circuit current; TongXie-YaoFang formula