Reduction in beta-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.
Fowler
C J
CJ
Department of Neuropharmacology, Astra Research Centre AB, Södertälje, Sweden.
Brännström
G
G
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C033394:CGP 12177; D003891:Desipramine