title: Abcb1 in Pigs: Molecular cloning, tissues distribution, functional analysis, and its effect on pharmacokinetics of enrofloxacin.
abstract: P-glycoprotein (P-gp) is one of the best-known ATP-dependent efflux transporters, contributing to differences in pharmacokinetics and drug-drug interactions. Until now, studies on pig P-gp have been scarce. In our studies, the full-length porcine P-gp cDNA was cloned and expressed in a Madin-Darby Canine Kidney (MDCK) cell line. P-gp expression was then determined in tissues and its role in the pharmacokinetics of oral enrofloxacin in pigs was studied. The coding region of pig Abcb1 gene was 3,861 bp, encoding 1,286 amino acid residues (Mw = 141,966). Phylogenetic analysis indicated a close evolutionary relationship between porcine P-gp and those of cow and sheep. Pig P-gp was successfully stably overexpressed in MDCK cells and had efflux activity for rhodamine 123, a substrate of P-gp. Tissue distribution analysis indicated that P-gp was highly expressed in brain capillaries, small intestine, and liver. In MDCK-pAbcb1 cells, enrofloxacin was transported by P-gp with net efflux ratio of 2.48 and the efflux function was blocked by P-gp inhibitor verapamil. High expression of P-gp in the small intestine could modify the pharmacokinetics of orally administrated enrofloxacin by increasing the Cmax, AUC and Ka, which was demonstrated using verapamil, an inhibitor of P-gp.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Tingting
authors: T
authors: Guo
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Jinhu
authors: J
authors: Huang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Hongyu
authors: H
authors: Zhang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Lingling
authors: L
authors: Dong
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Dawei
authors: D
authors: Guo
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Li
authors: L
authors: Guo
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Fang
authors: F
authors: He
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Zohaib Ahmed
authors: ZA
authors: Bhutto
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors: Liping
authors: L
authors: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003001:Cloning, Molecular; D004285:Dogs; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling; D007413:Intestinal Mucosa / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D010802:Phylogeny; D020112:Rhodamine 123 / Q000378:metabolism / Q000493:pharmacokinetics; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D024841:Fluoroquinolones; D020112:Rhodamine 123; D000077422:Enrofloxacin; D014700:Verapamil