PARA-CHLOROAMPHETAMINE INDUCES SEROTONIN RELEASE THROUGH SEROTONIN TRANSPORTERS
PARA-CHLOROAMPHETAMINE INDUCES SEROTONIN RELEASE THROUGH SEROTONIN TRANSPORTERS
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DOI：
10.1021/bi00144a010
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发表时间：
1992-07-28
期刊：
影响因子：
2.9
通讯作者：
WALL, SC
中科院分区：
文献类型：
--
作者：
RUDNICK, G;WALL, SC
p-Chloroamphetamine (PCA) interacts with serotonin transporters in two membrane vesicle model systems by competing with serotonin for transport and stimulating efflux of accumulated serotonin. In plasma membrane vesicles isolated from human platelets, PCA competes with [H-3]imipramine for binding to the serotonin transporter with a K(D) of 310 nM and competitively inhibits serotonin transport with a K(I) of 4.8 NM. [H-3]Serotonin efflux from plasma membrane vesicles is stimulated by PCA in a Na+-dependent and imipramine-sensitive manner characteristic of transporter-mediated exchange. In membrane vesicles isolated from bovine adrenal chromaffin granules, PCA competitively inhibits ATP-dependent [H-3]serotonin accumulation with a K(I) of 1.7-mu-M and, at higher concentrations, stimulates efflux of accumulated [H-3]serotonin. Stimulation of vesicular [H-3]serotonin efflux is due in part to dissipation of the transmembrane pH difference (DELTA-pH) generated by ATP hydrolysis. Part of PCA's ability to stimulate efflux may be due to its transport by the vesicular amine transporter. Flow dialysis experiments demonstrated uptake of [H-3]PCA into chromaffin granule membrane vesicles in response to the DELTA-pH generated in the presence of Mg2+ and ATP. In plasma membrane vesicles, no accumulation was observed using an NaCl gradient as the driving force. We conclude that rapid nonmediated efflux of transported PCA prevents accumulation unless PCA is trapped inside by a low internal pH.
