The α1-adrenergic photoaffinity probe [125I]arylazidoprazosin binds to a specific peptide of P-glycoprotein in multidrug-resistant cells

Ahmad Safa, Michael Agresti, Ikumi Tamai, Nitin D. Mehta, Soheila Vahabi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Much evidence suggests that P-glycoprotein (P-gp) confers multidrug-resistance (MDR) in tumor cells by energy-dependent efflux of hydrophobic cytotoxic agents. In this study, we have used the α1-adrenergic photoaffinity probe, [125I]arylazidoprazosin ([125I]AAP), and identified P-gp as a specific acceptor for prazosin. Drugs to which MDR cells are resistant, including vincristine, vinblastine, doxorubicin, actinomycin D and colchicine as well as agents reversing MDR, including verapamil, nicardipine, prenylamine, diltiazem, trifluoperazine, dibucaine, reserpine, monensin, and progesterone, differentially reduced [125I]AAP photolabeling of P-gp. We also analyzed the influence of α2-adrenergic drugs and dopaminergic drugs on [125I]AAP photolabeling of P-gp. Limited proteolysis of [125I]AAP photolabeled P-gp with Staphylococcus aureus V8 protease revealed that prazosin binds to a single 8 kDa fragment of P-gp.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume166
Issue number1
DOIs
StatePublished - Jan 15 1990
Externally publishedYes

Fingerprint

P-Glycoprotein
Adrenergic Agents
Peptides
Multiple Drug Resistance
Prazosin
Prenylamine
Dibucaine
Proteolysis
Nicardipine
Trifluoperazine
Monensin
Dopamine Agents
Vinblastine
Diltiazem
Reserpine
Cytotoxins
Colchicine
Dactinomycin
Vincristine
Verapamil

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The α1-adrenergic photoaffinity probe [125I]arylazidoprazosin binds to a specific peptide of P-glycoprotein in multidrug-resistant cells. / Safa, Ahmad; Agresti, Michael; Tamai, Ikumi; Mehta, Nitin D.; Vahabi, Soheila.

In: Biochemical and Biophysical Research Communications, Vol. 166, No. 1, 15.01.1990, p. 259-266.

Research output: Contribution to journalArticle

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