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 sensitive adenylate cyclase was investigated in human neuroblastoma SHSY-5Y cells. Incubation of SHSY-5Y cells in the presence of 100 nM retinoic acid (RA) for 24 hours resulted in phenotypic differentiation accompanied by a 47% increase in D2-receptor mRNA and a significant increase in the specific binding of a D2-receptor antagonist, [3H]YM09151-2. Stimulation of D2-receptors in differentiated cells by LY171-555, a D2-agonist, attenuated cellular cAMP levels by 30%. The effect of LY171-555 on cAMP levels was blocked by the D2-antagonist, (-)sulpride. Application of these drugs to control undifferentiated cells or differentiated cells incubated with vehicle only had no effect on cellular cAMP levels. These studies suggest that differentiated SHSY-5Y cells express functional D2-receptors and will provide a useful model for future studies on the regulation of expression and function of D2-receptors in cellular differentiation of neuronal cells.
Farooqui
S M
SM
Laboratory of Neurosciences, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001549:Benzamides / Q000378:metabolism; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D013469:Sulpiride / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001549:Benzamides; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D014212:Tretinoin; D013469:Sulpiride; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C030265:nemonapride