Differential effects of adrenaline and noradrenaline on the hepatic expression of immediate early genes in mice.
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.
Im
Y B
YB
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
Won
J S
JS
Suh
H W
HW
Huh
S O
SO
Kim
Y H
YH
Song
D K
DK
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
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