Reduction In Density Of Binding Sites Research Articles

Reduction in β‐Adrenoceptor Density in Cultured Rat Glioma C6 Cells After Incubation with Antidepressants Is Dependent upon the Culturing Conditions Used

The hydrophilic beta-adrenoceptor ligand (-)-[3H]CGP-12177 binds to intact C6 cells with a high affinity (KD approximately 0.1 nM) and with a high degree of specificity. The binding was inhibited by DL-propranolol (Ki approximately 1 nM). Treatment of cells cultured in Dulbecco's modified Eagle medium (DMEM) without fetal calf serum for 4 days with desipramine reduced the (-)-[3H]CGP-12177 specific binding in a concentration-dependent manner, a reduction from 127 to 102 fmol/mg of protein being found at a ligand concentration of 1 nM after treatment with 10 microM desipramine. Lesser effects were seen after treatment for 1 day. A similar result was found with maprotiline, and reductions in specific binding were seen after 4 days of treatment with amitriptyline, iprindole, and citalopram. The reduction in binding-site density (measured per milligram of protein to compensate for variability in cell density per well), however, was paralleled in all cases by a reduction in the rate of cell proliferation. When C6 glioma cells were cultured in Ham's medium without fetal calf serum during the antidepressant treatment period, a higher specific binding was observed than for the DMEM-cultured cells, and 10 microM desipramine was without effect on either the (-)-[3H]CGP-12177 specific binding or cell proliferation. It is concluded that the effects of the antidepressants tested upon the density of (-)-[3H]CGP-12177 specific binding sites in intact C6 cells may be secondary to the toxicity of the compounds under the conditions used.