Induction of adenylate cyclase sensitive dopamine D2-receptors in retinoic acid induced differentiated human neuroblastoma SHSY-5Y cells

Life Sci. 1994;55(24):1887-93. doi: 10.1016/0024-3205(94)00520-6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Base Sequence
  • Benzamides / metabolism
  • Cell Differentiation
  • Cyclic AMP / metabolism*
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / metabolism
  • Ergolines / pharmacology
  • Humans
  • Molecular Sequence Data
  • Neuroblastoma
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Quinpirole
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Second Messenger Systems
  • Sulpiride / pharmacology
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Benzamides
  • Dopamine Agonists
  • Dopamine Antagonists
  • Ergolines
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Quinpirole
  • Tretinoin
  • Sulpiride
  • Cyclic AMP
  • Adenylyl Cyclases
  • nemonapride