薬物の腸管吸収並びに腎排泄機構に関する分子・細胞生物学的解析

• 齋藤 秀之

書誌事項

タイトル別名

• Molecular and Cell Biological Analyses for Intestinal Absorption and Renal Excretion of Drugs
• ヤクブツ ノ チョウカン キュウシュウ ナラビニ ジン ハイセツ キコウ ニ

抄録

Intestinal absorption and renal tubular secretion are transport processes determining the availability and the disposition of drugs in the body. In this review, our studies on the molecular and cell biological analyses of intestinal absorption and renal secretion of drugs are described. We evaluated the transepithelial transport and the cellular accumulation of peptide-like drugs such as β-lactam antibiotics and bestatin (a dipeptide-like antineoplastic agent) in the human adenocarcinoma colon cell line, Caco-2, as an in vitro model for studying absorption mechanisms of these drugs. We have found that the transcellular transport of these peptide-like drugs is mediated by both the apically- and basolaterally-localized peptide transporters. To characterize molecular aspects of absorption of the peptide-like drugs, we studied cDNA cloning of H⁺/peptide cotransporters, PEPT1 and PEPT2, expressed in rats. The rat PEPT1 has been shown to mediate the H⁺-coupled uphill transport of β-lactam antibiotics across the brush-border membranes of the intestinal and renal epithelia. The rat PEPT2 is expressed predominantly in the kidney, but not in the intestine, mediating tubular reabsorption of the peptide-like drugs. We examined the transcellular transport of organic cations across monolayers of the kidney epithelial cell line, LLC-PK₁. We have found that LLC-PK₁ cells possess the H⁺/organic cation antiporter and the membrane potential-sensitive organic cation transporter in the apical and basolateral membranes, respectively, thereby tetraethylammonium (TEA) being transported unidirectionally from the basolateral to the apical side of the monolayers. We have isolated a cDNA encoding a rat kidney-specific organic cation transporter, OCT 2, which transports TEA in a H⁺-gradient independent manner, suggesting that OCT2 is localized to the basolateral membranes of renal tubular cells. In addition, a cDNA encoding a novel rat organic anion transporter, OAT-K1, has been cloned. OAT-K1 is expressed exclusively in the renal proximal tubules, and mediates the transport of methotrexate. Analyses of the molecular and cell biological mechanisms for drug absorption and secretion will provide information for the understanding of organspecific drug transport systems and for the development of drug design and/or drug delivery system.

収録刊行物

• 薬学雑誌

  薬学雑誌 117 (8), 522-541, 1997

  公益社団法人 日本薬学会

キーワード

• drug transport
• intestinal absorption
• renal tubular secretion
• peptide transporter
• β-lactam antibiotics
• organic anion

詳細情報

• CRID: 1390282681130699264
• NII論文ID: 110003649105
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi1947.117.8_522
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 4286490
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4286490
• Web Site: https://www.jstage.jst.go.jp/article/yakushi1947/117/8/117_8_522/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1998015746
• データソース種別:
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  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可