Effect of epinephrine and norepinephrine on zinc thionein levels and induction in rat liver

Abstract

Hepatic zinc metallothionein (MT) levels are increased in response to a variety of stresses. Glucocorticoid induction of zinc thionein is insufficient in accounting for the levels attained. The potential involvement of catecholamines in the modulation of rat hepatic zinc metabolism and zinc thionein levels has been systematically studied. Eleven hours after multiple injections (6) of epinephrine, norepinephrine, or isoproterenol, zinc thionein levels of 4.01 +/- 0.74, 6.83 +/- 0.67, and 11.75 +/- 0.96 micrograms Zn in MT/g liver, respectively, were attained (untreated, 1.04 +/- 0.14). The levels of hepatic zinc thionein thus reached the range of stress response-induced levels (4-10 micrograms Zn in MT/g liver), attained 11 h after the onset of the stress. Multiple injections of isoproterenol and norepinephrine induced the formation of isoforms MT-I and MT-II in roughly equal amounts. The alpha-adrenoceptor blocker phentolamine blocked the 11-h increase in norepinephrine-stimulated (6) zinc thionein levels by 88%. The beta-adrenoceptor blocker propranolol blocked the 11-h increase in isoproterenol-stimulated (6) zinc thionein levels by 55%. This inhibition could be increased to 72% by previous administration of both phentolamine and propranolol. Catecholamines stimulated increases in both the zinc and the protein of MT, the latter as assessed by [35S]cysteine incorporation. Both of these increases were blocked by cycloheximide, confirming the requirement for de novo protein synthesis in this induction response.

Regulation of metallothionein‐I+II levels in specific brain areas and liver in the rat: Role of catecholamines

“…Immobilization stress greatly increased liver MT concentrations, as expected (Hidalgo et al, 1988c(Hidalgo et al, , 1990(Hidalgo et al, , 1991a, but this was not affected by MPT, phentolamine, or propranolol, indicating that catecholamines were not involved in this response, despite the fact that exogenous catecholamines can induce liver MT synthesis (Brady and Helvig, 1984). This agrees with our previous results (Hidalgo et al, 1987, 198813) but not with others (Brady, 1981).…”

Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

“…Our present study shows that a single injection of a low dose (10 µg kg −1 ) of isoproterenol induced a transient hepatic, renal and cardiac MT induction. An induction of hepatic MT (12-fold) has been previously reported 11 h after six injections of 10 µg kg −1 Isp every 2 h (Brady and Helvig, 1984) which was in accordance with the 2-fold increase observed 12 h after a single injection.…”

“…The aim of this study was to investigate the capacity of cadmium and isoproterenol, two well-known inducers of MT in the liver (Brady, 1991;Brady and Helvig, 1984;Lazo et al, 1995;Kenaga et al, 1996;Iszard et al, 1995;Eaton et al, 1980;Klaassen and Liu, 1998;Onosaka and Cherian, 1981), to induce in vivo MT in the heart, aorta and kidney. In order to develop an experimental procedure for enhancing these tissue MT levels, different doses of Cd and isoproterenol and the time of responses were studied.…”

The ubiquitous role of zinc in health and disease

“…33 In the mammalian liver, synthesis of T is rapidly induced by a variety of factors including zinc (to a lesser degree by copper, cadmium, iron, mercury, and others), hormones (corticosteroids, glucagon, catecholamines), cytokines (interleukin-1 [IL-1], IL-6, and interferon [IFN]), oxidants, nitric oxide (NO), and angiotensin II. 5,[35][36][37] Ursodiol has also been shown to increase levels of MT in hepatocytes. 38 MT has been considered an acute phase protein because it is highly inducible with tissue injury, sepsis, inflammation, and neoplastic disease.…”