Effect of the Tricyclic Antidepressant Desipramine on β‐Adrenergic Receptors in Cultured Rat Glioma C6 Cells

Abstract

Rat glioma C6 cells, cultured in the presence of the tricyclic antidepressant desipramine, lost a significant number of .beta.-adrenergic receptors in a time- and dose-dependent manner. A similar loss was observed whether binding was determined on intact cells with the hydrophilic .beta.-adrenergic antagonist (.+-.)-[3H]4-(3-tert-butylamino-2-hydroxypropoxyl)benzimidazole- 2 - on HCl ([3H]CGP-12177) or on cell lysates with the more hydrophobic antagonists [125I]iodocyanopindolol or [3H]dihydroalprenolol. When stimulated with the agonist isoproterenol, desipramine-treated cells accumulated less cyclic AMP than control cells. The affinity of the .beta.-adrenergic receptors for either antagonist or agonist was unchanged after desipramine treatment. Desipramine interacted only weakly with the receptors and competed for [125I]iodocyanopindolol binding with a Ki of 30 .mu.M. The presence in the culture medium of alprenolol or propranolol, potent .beta.-adrenergic antagonists, however, did not prevent the reduction in receptors by desipramine. Desipramine also caused a loss of .beta.-adrenergic receptors from cells maintained in serum-free medium and the cells themselves did not contain or secrete endogenous catecholamines. Although desipramine is a potent inhibitor of catecholamine uptake, it appears unlikely that the observed loss of .beta.-adrenergic receptors in rat glioma C6 cells exposed to the drug is due to an increase in extracellular catecholamine levels or to a direct interaction with the receptors.