Characterization of [3H]paroxetine binding to rat cortical membranes.
Paroxetine is a selective and potent inhibitor of 5-hydroxytryptamine uptake into serotonergic neurons. The specific binding of [3H]paroxetine to rat cortical membranes at 22 degrees C was examined in this study. Our results indicate the presence of a single saturable high affinity binding component for [3H]paroxetine. Scatchard analysis revealed a Kd of 0.15 +/- 0.01 nM, and a Bmax of 549 +/- 36 fmol/mg protein. The kinetically derived dissociation constant was 0.034 +/- 0.008 nM. [3H]Paroxetine binding was inhibited selectively by 5-HT uptake blockers, and a good correlation was demonstrated between the potency of various drugs to inhibit [3H]paroxetine binding and [3H]5-hydroxytryptamine uptake. Also, lesions performed with the neurotoxin, 5,7-dihydroxytryptamine resulted in a 94% decrease in endogenous 5-hydroxytryptamine levels and concomitantly, a 90% reduction in [3H]paroxetine binding when compared to sham controls. These results indicate that the binding site labelled by [3H]paroxetine is associated with the neuronal 5-hydroxytryptamine transporter complex.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism
D010880:Piperidines; D011985:Receptors, Serotonin; D017374:Paroxetine