INDUCTION OF ADENYLATE-CYCLASE SENSITIVE DOPAMINE D2-RECEPTORS IN RETINOIC ACID-INDUCED DIFFERENTIATED HUMAN NEUROBLASTOMA SHSY-5Y CELLS

Dopamine D2 receptor (D2-receptor) expression and its coupling to Gi s ensitive adenylate cyclase was investigated in human neuroblastoma SHS Y-5Y cells. Incubation of SHSY-5Y cells in the presence of 100 nM reti noic acid (RA) for 24 hours resulted in phenotypic differentiation acc ompanied by a 47% increase in D2-receptor mRNA and a significant incre ase in the specific binding of a D2-receptor antagonist, [H-3]YM09151- 2. Stimulation of D2-receptors in differentiated cells by LY171-555, a D2-agonist, attenuated cellular cAMP levels by 30%. The effect of LY1 71-555 on cAMP levels was blocked by the D2-antagonist, (-)sulpride. A pplication of these drugs to control undifferentiated cells or differe ntiated cells incubated with vehicle only had no effect on cellular cA MP levels. These studies suggest that differentiated SHSY-5Y cells exp ress functional D2-receptors and will provide a useful model for futur e studies on the regulation of expression and function of D2-receptors in cellular differentiation of neuronal cells.