Differentiation-associated decrease in muscarinic receptor sensitivity in human neuroblastoma cells

Muscarinic receptor-linked increases in intracellular free Ca2+ as measured with quin-2 and Ca2+ release from monolayers of cells have been measured in the human neuroblastoma cell line SH-SY5Y. Induction of differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to a decrease in the sensitivity of the cells to low concentrations of agonists with respect to the induced increase in cytosolic free Ca2+ and stimulation of Ca2+ efflux. No decrease in agonist binding affinity was observed when the displacement of a labelled antagonist, 3H-NMS, by a non-labelled agonist was studied.