Differential coupling of muscarinic receptors to Ca2+ mobilization and cyclic AMP in SH-SY5Y and IMR 32 neuroblastoma cells

doi:10.1016/0922-4106(91)90045-J

European Journal of Pharmacology: Molecular Pharmacology

Volume 208, Issue 1, 12 September 1991, Pages 9-15

https://doi.org/10.1016/0922-4106(91)90045-J Get rights and content

Abstract

Muscarinic receptor-linked Ca²⁺ mobilization and changes in cyclic AMP were studied in SH-SY5Y and IMR 32 human neuroblastoma cell lines. Muscarinic agonists acetylcholine, carbachol, methacholine and muscarine induced an increase in cytosolic free Ca²⁺ in a pertussis toxin (100 ng/ml)-insensitive manner in both cell lines. The ED₅₀ values in IMR 32 cells (8–98 μM) were one order of magnitude higher than in SH-SY5Y cells (0.3 – 1.6 μM). Oxotremorine and pilocarpine failed to mobilize Ca²⁺ in IMR 32 cells. Pirenzepine antagonized carbachol-induced Ca²⁺ mobilization in SH-SY5Y cells with a K_i value in the range of 150–189 nM whereas the corresponding values in IMR 32 cells were 24–28 nM. Atropine inhibited a carbachol-stimulated increase in cytosolic Ca²⁺ with an equal potency in both cell lines (K_i 2–3 nM). Carbachol stimulated cyclic AMP (cAMP) accumulation in SH-SY5Y cells in a pertussis toxin-insensitive manner. In IMR 32 cells carbachol inhibited prostaglandin E₁-stimulated cAMP accumulation. Treatment of IMR 32 cells with pertussis toxin abolished the inhibition of stimulated cAMP accumulation. These results suggest that in SH-SY5Y cells the M₃ muscarinic receptor couples to both Ca²⁺ mobilization and stimulation of cAMP accumulation. In IMR 32 cells the M₁ receptor seems to couple to Ca²⁺ mobilization whereas the inhibition of stimulated cAMP accumulation is coupled to a non-M₁ subtype by an inhibitory G-protein.

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Differential coupling of muscarinic receptors to Ca2+ mobilization and cyclic AMP in SH-SY5Y and IMR 32 neuroblastoma cells

Abstract

FEBS Lett.

Cell

Biochem. Biophys. Res. Commun.

FEBS Lett.

Brain Res.

Neurochem. Int.

J. Biol. Chem.

Eur. J. Pharmacol.

Brain Res.

Brain Res.

FEBS Lett.

Biochem. Biophys. Res. Commun.

Muscarinic receptor-stimulated phosphoinositide turnover in human SK-N-SH neuroblastoma cells: differential inhibition by agents that elevate cyclic AMP

J. Neurochem.

α2-Adrenergic and muscarinic cholinergic receptors have opposing actions on cyclic AMP levels in SK-N-SH human neuroblastoma cells

J. Neurochem.

Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture

Cancer Res.

Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones

Cancer Res.

Differential coupling of muscarinic receptors to Ca²⁺ mobilization and cyclic AMP in SH-SY5Y and IMR 32 neuroblastoma cells

α₂-Adrenergic and muscarinic cholinergic receptors have opposing actions on cyclic AMP levels in SK-N-SH human neuroblastoma cells