Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines

Tomoya Okada, Masahiro Fujita, Shoichi Shimada, Kohji Sato, Patrick Schloss, Yoshiyuki Watanabe, Yasushi Itoh, Masaya Tohyama, Tsunehiko Nishimura

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We investigated the effects of three cocaine analogs, beta-CIT (2-beta- carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta- carbomethoxy-3-beta-(4-iodophenyl)-N-(2-fluoroethyl)-nortropane), and beta- CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)- nortropane), on the uptake of [3H]dopamine(DA), serotonin(5-HT), and 1- norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [3H]DA, 5-HT, and 1-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [3H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta- CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET).

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalNuclear Medicine and Biology
Volume25
Issue number1
DOIs
StatePublished - Jan 1998

Keywords

  • Beta-CIT-FP
  • Cell line
  • Cocaine
  • Dopamine transporter
  • SPECT

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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