Additive induction of Egr-1 (zif/268) mRNA expression in neuroblastoma x glioma hybrid NG108-15 cells via cholinergic muscarinic, alpha 2-adrenergic, and bradykinin receptors.
Administration of carbachol, noradrenaline, and bradykinin induced Egr-1 mRNA expression within 1 h in mouse neuroblastoma x rat glioma hybrid NG108-15 cells. With specific receptor antagonists, the Egr-1 inductions by carbachol and noradrenaline were shown to be mediated via cholinergic muscarinic and alpha 2-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.
Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
N
N
Katayama
E
E
Iwata
H
H
Sakurai
T
T
Tsuchiya
M
M
Tsuda
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000378:metabolism; D006822:Hybrid Cells / Q000378:metabolism; D017874:Immediate-Early Proteins; D009447:Neuroblastoma / Q000378:metabolism; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D018002:Receptors, Bradykinin; D011976:Receptors, Muscarinic / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D018002:Receptors, Bradykinin; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin