TY - JOUR
T1 - Amphetamine derivatives interact with both plasma membrane and secretory vesicle biogenic amine transporters
AU - Schuldiner, Shimon
AU - Steiner-Mordoch, Sonia
AU - Yelin, Rodrigo
AU - Wall, Stephen C.
AU - Rudnick, Gary
PY - 1993/12
Y1 - 1993/12
N2 - The interaction of fenfluramine, 3,4-methylenedioxymethamphetamine (MDMA), and p-chloroamphetamine (PCA) with the platelet plasma membrane serotonin transporter and the vesicular amine transporter were studied using both transport and binding measurements. Fenfluramine is apparently a substrate for the plasma membrane transporter, and consequently inhibits both serotonin transport and imipramine binding. Moreover, fenfluramine exchanges with internal [3H]serotonin in a plasma membrane transporter-mediated reaction that requires NaCl and is blocked by imipramine. These properties are similar to those of MDMA and PCA as previously described. In adrenal chromaffin granule membrane vesicles containing the vesicular amine transporter, fenfluramine inhibited serotonin transport and dissipated the transmembrane pH difference (ΔpH) that drives amine uptake. The use of [3H]reserpine-binding measurements to determine drug interaction with the vesicular amine transporter allowed assessment of the relative ability of MDMA, PCA, and fenfluramine to bind to the substrate site of the vesicular transporter. These measurements permit a distinction between inhibition of vesicular serotonin transport by directly blocking vesicular amine transport and by dissipating ΔpH. The results indicate that MDMA and fenfluramine inhibit by both mechanisms but PCA dissipates ΔpH without blocking vesicular amine transport directly.
AB - The interaction of fenfluramine, 3,4-methylenedioxymethamphetamine (MDMA), and p-chloroamphetamine (PCA) with the platelet plasma membrane serotonin transporter and the vesicular amine transporter were studied using both transport and binding measurements. Fenfluramine is apparently a substrate for the plasma membrane transporter, and consequently inhibits both serotonin transport and imipramine binding. Moreover, fenfluramine exchanges with internal [3H]serotonin in a plasma membrane transporter-mediated reaction that requires NaCl and is blocked by imipramine. These properties are similar to those of MDMA and PCA as previously described. In adrenal chromaffin granule membrane vesicles containing the vesicular amine transporter, fenfluramine inhibited serotonin transport and dissipated the transmembrane pH difference (ΔpH) that drives amine uptake. The use of [3H]reserpine-binding measurements to determine drug interaction with the vesicular amine transporter allowed assessment of the relative ability of MDMA, PCA, and fenfluramine to bind to the substrate site of the vesicular transporter. These measurements permit a distinction between inhibition of vesicular serotonin transport by directly blocking vesicular amine transport and by dissipating ΔpH. The results indicate that MDMA and fenfluramine inhibit by both mechanisms but PCA dissipates ΔpH without blocking vesicular amine transport directly.
UR - http://www.scopus.com/inward/record.url?scp=0027731280&partnerID=8YFLogxK
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C2 - 7903417
AN - SCOPUS:0027731280
SN - 0026-895X
VL - 44
SP - 1227
EP - 1231
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 6
ER -