nafadotride and Glioma

Topics: Animals; Cell Division; Cell Line; Cyclic AMP; Dopamine Agonists; Ergolines; Gene Expression; Glioma; Models, Biological; Naphthalenes; Neuroblastoma; Neurotensin; Nucleus Accumbens; Pyrrolidines; Quinpirole; Receptors, Dopamine D2; Receptors, Dopamine D3; Recombinant Proteins; Transfection

In NG 108-15 cells expressing the recombinant human D3 receptor, dopamine agonists enhance [3H]thymidine incorporation and decrease cAMP accumulation. In these cells, but not in wild type cells, haloperidol, fluphenazine, and various other antipsychotics inhibited basal [3H]thymidine incorporation in a concentration-dependent manner. In contrast, other dopamine antagonists such as nafadotride or (+)AJ 76, two D3-preferring antagonists, were without effect. The concentration-response curve of haloperidol was shifted to the right in presence of nafadotride, with a potency compatible with its nanomolar apparent affinity as neutral antagonist. Pertussis toxin treatment abolished or markedly reduced the responses to haloperidol or fluphenazine. In contrast, no significant enhancement of cAMP accumulation could be observed, under the influence of haloperidol or eticlopride. These data indicate that some dopamine antagonists behave as inverse agonists, and thus appear to inhibit an agonist-independent activity of the D3 receptor on [3H]thymidine incorporation pathway, but not on the cAMP pathway.

Topics: Animals; Antipsychotic Agents; Calcium; CHO Cells; Clozapine; Colforsin; Cricetinae; Cyclic AMP; DNA Replication; Dopamine Agonists; Dopamine Antagonists; Dose-Response Relationship, Drug; Flupenthixol; Glioma; Haloperidol; Humans; Hybrid Cells; Naphthalenes; Neuroblastoma; Pertussis Toxin; Phenothiazines; Pimozide; Pyrrolidines; Quinpirole; Receptors, Dopamine D2; Receptors, Dopamine D3; Recombinant Proteins; Risperidone; Salicylamides; Second Messenger Systems; Sulpiride; Tetrahydronaphthalenes; Tumor Cells, Cultured; Virulence Factors, Bordetella