title: Contribution of TRPV1 and multidrug resistance proteins in the permeation of capsaicin across different intestinal regions.
abstract: OBJECTIVE
  The aim of the study was to observe the characteristic of permeation of capsaicin across jejunum, ileum and colon in the rat, and to investigate the role of transient receptor potential cation channel (TRPV1). The interaction of capsaicin with P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) was also investigated.
  
  
  METHODS
  The transport of capsaicin across three intestinal segments in rats was investigated using Ussing-chamber System.
  
  
  RESULTS
  The permeability of capsaicin across the colonic ileac or jejunal membrane was significantly different in M-S direction (11.679 ± 2.001, 5.336 ± 1.248, 1.395 ± 0.673, ×10(-6)cm/s). TRPV1 non-competitive antagonist ruthenium red significantly decreased the permeability of capsaicin in M-S direction across colonic membrane. The permeability of capsaicin could also be inhibited unconventionally by the BCRP inhibitor novobiocin in M-S direction across colon. However, either the P-gp inhibitor verapamil or the MRP2 inhibitor probenecid did not affect the transport of capsaicin in all three segments.
  
  
  CONCLUSIONS
  We firstly proved that the permeability of capsaicin across colon was significantly higher than that across jejunum or ileum. Furthermore, TRPV1 might mediate the transport of capsaicin across the intestinal membrane. Therefore, the colon-specific highest permeation of capsaicin could be the consequence of the colon-specific distribution of TRPV1. For another, there may be another transport pathway mediating the permeation of capsaicin in M-S direction, which could be inhibited by novobiocin.
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors: Lian
authors: L
authors: Duan
authors: Yuan
authors: Y
authors: Yan
authors: YaBin
authors: Y
authors: Sun
authors: Boxin
authors: B
authors: Zhao
authors: WenJun
authors: W
authors: Hu
authors: GuoFeng
authors: G
authors: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D041741:Lower Gastrointestinal Tract / Q000378:metabolism*; D008297:Male; D009675:Novobiocin / Q000494:pharmacology; D010539:Permeability; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; C489249:Abcg2 protein, rat; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; D009675:Novobiocin; D014700:Verapamil; D011339:Probenecid; D002211:Capsaicin