Premium
Serotonergic Antagonist Effects on Trafficking of Serotonin 5‐HT 2A Receptors in Vitro and in Vivo a
Author(s) -
WILLINS D. L.,
ALSAYEGH L.,
BERRY S. A.,
BACKSTROM J. R.,
SANDERSBUSH E.,
FRIEDMAN L.,
KHAN N.,
ROTH B. L.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10182.x
Subject(s) - intracellular , in vivo , receptor , serotonergic , 5 ht receptor , internalization , serotonin , microbiology and biotechnology , chemistry , in vitro , pharmacology , biology , biochemistry
The mechanism by which antagonists down‐regulate 5‐HT 2A receptors is unknown. We here report that a variety of 5‐HT 2A antagonists induce a change in the subcellular distribution of 5‐HT 2A receptors both in vitro and in vivo . In a stably transfected NIH 3T3 cell‐line, brief exposure to 1 μM clozapine caused a 2.5‐fold increase in intracellular 5‐HT 2A ‐like immunoreactivity, as measured by confocal microscopy. Confirmatory studies utilizing a biotin‐trap technique, demonstrated that the increase in intracellular immunoreactivity results from internalization of receptor from the cell surface. Exposure of transfected cells to other 5‐HT 2A receptor antagonists produced similar increases in intracellular 5‐HT 2A ‐like immunoreactivity. In vivo administration of clozapine (20 mg/kg, sc, ×7 days) caused a greater than twofold increase in intracellular immunoreactivity in cell bodies of cortical pyramidal neurons. Additionally, chronic clozapine administration was associated with a decrease in labeling of apical dendrites on pyramidal cells. These results show that clozapine causes a change in subcellular distribution of 5‐HT 2A receptors in vitro and in vivo .