Additive Induction of Egr‐1 (zif/268) mRNA Expression in Neuroblastoma × Glioma Hybrid NG108‐15 Cells via Cholinergic Muscarinic, α₂‐Adrenergic, and Bradykinin Receptors

Abstract: Administration of carbachol, noradrenaline, and bradykinin induced Egr‐1 mRNA expression within 1 h in mouse neuroblastoma × rat gliomahybrid NG108–15 cells. With specific receptor antagonists, the Egr‐1 inductions by carbachol and noradrenaline were shown to be mediated via cholinergic muscarinic and α₂‐adrenergic receptors, respectively. At their saturation levels for Egr‐1 induction, the two agonists had additive effects when added together, but no prolongation of the effect on Egr‐1 induction was observed. Addition of carbachol or noradrenaline 6 h after primary stimulation with carbachol or noradrenaline did not result in secondary Egr‐1 induction, probably because of receptor desensitization. On the other hand, bradykinin consistently had an additive effect on Egr‐1 induction, irrespective of the time of its addition, suggesting that the signal pathways for Egr‐1 induction by carbachol or noradrenaline and by bradykinin are different. Treatment of cells with pertussis toxin or cholera toxin strongly inhibited Egr‐1 induction by carbachol or noradrenaline but only partially inhibited the induction by bradykinin. Thus, the signals transduced in NG108–15 cells by different neurotransmitter receptors appear to have different effects on Egr‐1 induction, depending on the times of stimulation and the combinations of receptors stimulated.