Interaction of organic chemicals with P-glycoprotein in the adrenal gland, kidney, and a multidrug-resistant KB cell

Misako Ichikawa, Akihiko Yoshimura, Tomoyuki Sumizawa, Norimasa Shudo, Yasuo Kuwazuru, Tatsuhiko Furukawa, Shin Ichi Akiyama

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

P-glycoprotein (P-gp) is thought to mediate the transport of anti-cancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype in tumor cells. However, the function of P-gp in normal tissues is still not well understood. We present evidence indicating that the active efflux of several structurally unrelated organic compounds is mediated by P-gp in multidrug-resistant KB (KB-C2) cells and that these compounds interact with P-gp in the kidney and adrenal gland. The photoactive radioactive calcium channel blocker [3H]azidopine labels a protein of ∼140 kDa in crude membrane fractions from human kidney and adrenal gland and a 130-kDa protein from bovine adrenal gland. These photolabeled proteins are immunoprecipitated with an anti-P-gp antibody. Photolabeling is inhibited by vinblastine, reserpine, and several other organic chemicals. These data indicate that the kidney and adrenal gland express P-gp (or a protein closely related to P-gp) that can interact with several organic compounds and that the P-gp expressed in these tissues has a drug-binding site similar to that of P-gp in KB-C2 cells. Our findings thus strongly support the hypothesis that P-gp can transport a wide variety of organic chemicals as well as anti-cancer drugs and that one of the physiological functions of P-gp is the excretion of certain classes of organic compounds.

Original languageEnglish
Pages (from-to)903-908
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number2
Publication statusPublished - 1991 Jan 15
Externally publishedYes

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Organic Chemicals
KB Cells
P-Glycoprotein
Adrenal Glands
Kidney
Organic compounds
Proteins
Pharmaceutical Preparations
Tissue
Neoplasms
Vinblastine
Reserpine
Calcium Channel Blockers
Labels
Tumors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ichikawa, M., Yoshimura, A., Sumizawa, T., Shudo, N., Kuwazuru, Y., Furukawa, T., & Akiyama, S. I. (1991). Interaction of organic chemicals with P-glycoprotein in the adrenal gland, kidney, and a multidrug-resistant KB cell. Journal of Biological Chemistry, 266(2), 903-908.

Interaction of organic chemicals with P-glycoprotein in the adrenal gland, kidney, and a multidrug-resistant KB cell. / Ichikawa, Misako; Yoshimura, Akihiko; Sumizawa, Tomoyuki; Shudo, Norimasa; Kuwazuru, Yasuo; Furukawa, Tatsuhiko; Akiyama, Shin Ichi.

In: Journal of Biological Chemistry, Vol. 266, No. 2, 15.01.1991, p. 903-908.

Research output: Contribution to journalArticle

Ichikawa, M, Yoshimura, A, Sumizawa, T, Shudo, N, Kuwazuru, Y, Furukawa, T & Akiyama, SI 1991, 'Interaction of organic chemicals with P-glycoprotein in the adrenal gland, kidney, and a multidrug-resistant KB cell', Journal of Biological Chemistry, vol. 266, no. 2, pp. 903-908.
Ichikawa, Misako ; Yoshimura, Akihiko ; Sumizawa, Tomoyuki ; Shudo, Norimasa ; Kuwazuru, Yasuo ; Furukawa, Tatsuhiko ; Akiyama, Shin Ichi. / Interaction of organic chemicals with P-glycoprotein in the adrenal gland, kidney, and a multidrug-resistant KB cell. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 2. pp. 903-908.
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