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 (alpha(1)-adrenergic antagonist; 0.5 mg kg(-1), i.p.), but not with yohimbine (alpha(2)-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 (beta(2)-adrenoceptor antagonist; 2 mg kg(-1), i.p.), but not betaxolol (beta(1)-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 alpha(1)-adrenergic receptors, whereas in the case of adrenaline, this is elicited by stimulating both alpha(1)- and beta(2)-adrenergic receptors in mice. These catecholamine-induced hepatic IEG responses may be responsible for mediating some of the catecholamine actions in the liver.