[3H] sertraline binding to rat brain membranes |
| |
Authors: | B K Koe L A Lebel W M Welch |
| |
Institution: | (1) Central Research Division, Pfizer Inc., 06340 Groton, CT, USA;(2) Department of Pharmacology, Pifzer Inc., 06340 Groton, CT, USA |
| |
Abstract: | Tritiated sertraline, a radiolabeled form of a potent and selective inhibitor of serotonin uptake, was found to bind with high affinity to rat whole brain membranes. Characterization studies showed that 3H] sertraline binding occurred at a single site with the following parameters:K
d
0.57 nM,B
max 821 fmol/mg protein,n
h
1.06. This binding was reversible; the dissociation constant calculated from kinetic measurements (K
d
0.81 nM) agreed with that determined by saturation binding experiments. 3H] Sertraline binding in the presence of serotonin, paroxetine, fluoxetine or imipramine suggested competitive inhibition of binding (large increase inK
d
with little change inB
max). The rank order of potency of inhibition of 3H] sertraline binding was similar to that of inhibition of serotonin uptake for known uptake inhibitors and the 1-amino-4-phenyltetralin uptake blockers. A marked decrease in ex vivo 3H] sertraline binding in the brain of rats 7 days after treatment withp-chloroamphetamine was consistent with the loss of serotonin uptake sites induced by this agent. The results of our study indicated that 3H] sertraline labels serotonin uptake sites in rat brain. |
| |
Keywords: | [3H] Sertraline binding Serotonin uptake Uptake blockers 1-Amino-4-phenyltetralins |
本文献已被 SpringerLink 等数据库收录! |
|