title: Differential effects of adrenaline and noradrenaline on the hepatic expression of immediate early genes in mice.
abstract: 1. The effects of intraperitoneally (i.p.) administered noradrenaline and adrenaline on the hepatic expression of immediate early genes (IEGs) were studied in mice. 2. Intraperitoneal injections of various doses (0.2-2 mg kg(-1)) of noradrenaline and adrenaline dose-dependently induced hepatic c-fos and c-jun mRNA levels. The time-course study showed that there was an increase in c-fos and c-jun mRNA levels within 15 min, which reached a peak at 30 min, and returned to the basal levels 1-2 h after noradrenaline or adrenaline injection (2 mg kg(-1), i.p.). A Western blot assay revealed that c-Jun protein levels were maximally increased at 30 min and 1-2 h in noradrenaline- and adrenaline-treated mice, respectively. There was a slight increase in c-Fos protein, while 46-kDa Fra protein was prominently increased. Noradrenaline (2 mg kg(-1), i.p.) induced 46-kDa Fra within 15 min, which reached a maximum at 30 min and returned to the basal levels by 1 h. Adrenaline (2 mg kg(-1), i.p.) induced 46-kDa Fra at 30 min, which returned to the basal levels at 4 h. 3. Noradrenaline (2 mg kg(-1), i.p.)-induced increases in c-fos and c-jun mRNA expressions were inhibited by the pre-treatment with prazosin (alpha1-adrenergic antagonist; 0.5 mg kg(-1), i.p.), but not with yohimbine (alpha2-adrenoceptor antagonist; 1 mg kg(-1), i.p.) nor with propranolol (beta-adrenoceptor antagonist; 10 mg kg(-1), i.p.). Adrenaline (2 mg kg(-1), i.p.)-induced increases in c-fos and c-jun mRNA expressions were inhibited by the pre-treatment with prazosin or with propranolol, but not with yohimbine. Administration of ICI-118,551 (beta2-adrenoceptor antagonist; 2 mg kg(-1), i.p.), but not betaxolol (beta1-adrenoceptor antagonist; 2 mg kg(-1), i.p.), blocked adrenaline (2 mg kg(-1), i.p.)-induced increases in c-fos and c-jun mRNA expressions. 4. The results suggest that noradrenaline elicits the hepatic c-fos and c-jun mRNA responses by stimulating alpha1-adrenergic receptors, whereas in the case of adrenaline, this is elicited by stimulating both alpha1- and beta2-adrenergic receptors in mice. These catecholamine-induced hepatic IEG responses may be responsible for mediating some of the catecholamine actions in the liver.
authors.affiliation: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
authors.forename: Y B
authors.initials: YB
authors.lastname: Im
authors.forename: J S
authors.initials: JS
authors.lastname: Won
authors.forename: H W
authors.initials: HW
authors.lastname: Suh
authors.forename: S O
authors.initials: SO
authors.lastname: Huh
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: D K
authors.initials: DK
authors.lastname: Song
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D051921:Fos-Related Antigen-2; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D009638:Norepinephrine; D004837:Epinephrine