TY - JOUR
T1 - Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines
AU - Okada, Tomoya
AU - Fujita, Masahiro
AU - Shimada, Shoichi
AU - Sato, Kohji
AU - Schloss, Patrick
AU - Watanabe, Yoshiyuki
AU - Itoh, Yasushi
AU - Tohyama, Masaya
AU - Nishimura, Tsunehiko
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/1
Y1 - 1998/1
N2 - 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).
AB - 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).
KW - Beta-CIT-FP
KW - Cell line
KW - Cocaine
KW - Dopamine transporter
KW - SPECT
UR - http://www.scopus.com/inward/record.url?scp=0031986219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031986219&partnerID=8YFLogxK
U2 - 10.1016/S0969-8051(97)00156-X
DO - 10.1016/S0969-8051(97)00156-X
M3 - Article
C2 - 9466362
AN - SCOPUS:0031986219
SN - 0969-8051
VL - 25
SP - 53
EP - 58
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 1
ER -