Kinetic Effects of Terbium Ions on Muscarinic Acetylcholine Receptors of Murine Neuroblastoma Cells

Abstract

Preincubation of murine neuroblastoma cells (clone NIE‐115) with terbium chloride resulted in a significant potentiation of carbachol‐mediated increase in cyclic GMP formation. This effect was accompanied by a shift of the peak response from 30 s to 120 s and a 6‐fold decrease in carbachol concentration producing half‐maximal responses, in addition to a significant increase in the Hill coefficient. Terbium ions also caused a significant decrease in the affinity and an increase in the maximum binding of [³H]quinuclidinyl benzilate to muscarinic receptors, the change in affinity being mainly due to a decrease in the association rate. Preincubation of cells with 1 mM carbachol for 4 h (the desensitized state of the muscarinic receptor) resulted in a decrease in the ability of terbium to alter [³H]quinuclidinyl benzilate binding. The effects of terbium reported here might be due to its affecting muscarinic receptor‐effector coupling, which is considered to be lost upon receptor desensitization.