Aquaporin 8 is involved in H O -mediated differential regulation of metabolic signaling by α - and β-adrenoceptors in hepatocytes.

Reactive oxygen species participate in regulating intracellular signaling pathways. Herein, we investigated the reported opposite effects of hydrogen peroxide (H O ) on metabolic signaling mediated by activated α - and β-adrenoceptors (ARs) in hepatocytes. In isolated rat hepatocytes, stimulation of α -AR increases H O production via NADPH oxidase 2 (NOX2) activation.

β- Adrenoceptors activate hepatic glutathione efflux through an unreported pathway.

The physiological regulation of hepatic glutathione efflux by catecholamines is poorly understood. The purpose of this work was to review the role of adrenergic receptors (AR) on total glutathione (G) efflux in rat liver. Two models were used: isolated hepatocytes and perfused livers.

Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity.

Spatiotemporal regulation of cAMP within the cell is required to achieve receptor-specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP-responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own nondiffusible (sequestered) cAMP pool to achieve their specific responses.

NOX2 activated by α1-adrenoceptors modulates hepatic metabolic routes stimulated by β-adrenoceptors.

The NADPH oxidase (NOX) family of enzymes oxidase catalyzes the transport of electrons from NADPH to molecular oxygen and generates O(2)(•-), which is rapidly converted into H(2)O(2). We aimed to identify in hepatocytes the protein NOX complex responsible for H(2)O(2) synthesis after α(1)-adrenoceptor (α(1)-AR) stimulation, its activation mechanism, and to explore H(2)O(2) as a potential modulator of hepatic metabolic routes, gluconeogenesis, and ureagenesis, stimulated by the ARs. The dormant NOX2 complex present in hepatocyte plasma membrane (HPM) contains gp91(phox), p22(phox), p40(phox), p47(phox), p67(phox) and Rac 1 proteins.

Evidence that endogenous inosine and adenosine-mediated hyperglycaemia during ischaemia-reperfusion through A3 adenosine receptors.

1 The molecular mechanism underlying stress-induced hyperglycemia has not been comprehensively clarified. Recently, we demonstrated in ischaemia-reperfusion (I-R) stress-subjected liver that inosine and adenosine are mainly responsible for the hyperglycemia observed. 2 We aimed to advance in the knowledge of the role of inosine plus adenosine as mediators of hepatic-induced hyperglycemia detected after I-R in lower limbs.

Adrenaline stimulates H2O2 generation in liver via NADPH oxidase.

It is known that adrenaline promotes hydroxyl radical generation in isolated rat hepatocytes. The aim of this work was to investigate a potential role of NADPH oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline in hepatocytes. Enriched plasma membranes from isolated rat liver cells were prepared for this purpose.

In rat hepatocytes, different adenosine receptor subtypes use different secondary messengers to increase the rate of ureagenesis.

In rat hepatocytes, the role of cAMP and Ca(2+) as secondary messengers in the ureagenic response to stimulation of specific adenosine receptor subtypes was explored. Analyzed receptor subtypes were: A(1), A(2A), A(2B) and A(3). Each receptor subtype was stimulated with a specific agonist while blocking all other receptor subtypes with a battery of specific antagonists.

Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors.

Inosine, an endogenous nucleoside, has recently been shown to exert potent effects on the immune, neural, and cardiovascular systems. This work addresses modulation of intermediary metabolism by inosine through adenosine receptors (ARs) in isolated rat hepatocytes. We conducted an in silico search in the GenBank and complete genomic sequence databases for additional adenosine/inosine receptors and for a feasible physiological role of inosine in homeostasis.

Prophylactic action of lipoic acid on oxidative stress and growth performance in broilers at risk of developing ascites syndrome.

The objective of this study was to assess the effects of dietary supplementation with lipoic acid (LA) on broilers maintained at 2235 m above sea level with high risk to develop ascites syndrome (AS). A total of 2040 chicks were fed under commercial conditions with water and specific diets ad libitum during 7 weeks in two consecutive experiments. Mortality and indicators of performance and oxidative stress were compared weekly in broilers fed a basal diet plus 0, 10, 20, or 40 parts/10(6) LA.

Adrenaline (via alpha(1B)-adrenoceptors) and ethanol stimulate OH* radical production in isolated rat hepatocytes.

Adrenaline is able to increase the oxidative damage caused by some xenobiotic agents in the liver. Ethanol produces oxidative changes in hepatic tissue, while an acute intoxication with alcohol increases adrenaline blood levels. The aim of this study was to determine whether adrenaline increases ethanol-induced hydroxyl free radical production in isolated hepatocytes.

Effects of dietary supplementation with vitamin C or vitamin E on cardiac lipid peroxidation and growth performance in broilers at risk of developing ascites syndrome.

Objective: To assess effects of high dietary amounts of vitamin C or vitamin E and oxidative stress on the heart and growth performance of broilers maintained at an altitude of 2,200 m above sea level.

Animals: 360 chicks (1-day-old broilers).

Procedure: Birds were randomly assigned to 3 groups (120 chicks/group).

Regulation of glycogen metabolism in hepatocytes through adenosine receptors. Role of Ca2+ and cAMP.

The objective of this work is to identify the adenosine receptor subtype and the triggered events involved in the regulation of hepatic glycogen metabolism. Glycogenolysis, gluconeogenesis, cAMP, and cytosolic Ca2+ ([Ca2+](cyt)) were measured in isolated hepatocytes challenged with adenosine A1, A2A, and A3 receptor-selective agonists. Stimulation of adenosine receptor subtypes with selective agonists in Ca2+ media produced a dose-dependent increase in [Ca2+]cyt with A1>A2=A3, cAMP with A2A, glycogenolysis with A1>A2A>A3, and gluconeogenesis with A2A>A1>A3, in addition, a decrease in cAMP was observed with A1=A3.

Antagonism between the metabolic responses induced by epinephrine and piroxicam on isolated rat hepatocytes.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most employed therapeutic agents. They have a wide spectrum of biological effects, some of which are independent of cyclooxygenase inhibition, such as the alterations on the components of signal transduction systems. In particular, previous data from our laboratory suggested an antagonism between epinephrine and piroxicam, one of the most prescribed NSAIDs.

Ca2+ dependence of the response of three adenosine type receptors in rat hepatocytes.

The effect of three different receptor-specific adenosine agonists on the rate of ureagenesis by isolated rat hepatocytes and the dependence on the external free Ca2+ concentration ([Ca2+]e) were investigated. In the presence of high [Ca2+]e all adenosine receptor agonists increased ureagenesis to similar levels. However, with low [Ca2+]e the effects of each agonist varied as follows: (i) the adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine, increased ureagenesis depending partially on [Ca2+]e, (ii) the adenosine receptor A2 agonist, 2-p-(-2-carboxy-ethyl) phenethylamino-5'-N-ethylcarboxyamido adenosine hydrochloride, increased ureagenesis independently of [Ca2+]e and (iii) in contrast, the adenosine receptor A3 agonist N6-2-(-4-aminophenyl) ethyladenosine, increased ureagenesis only in the presence of high [Ca2+]e.

Piroxicam modifies the effects of ethanol on isolated rat hepatocytes.

It has been reported that piroxicam prevents the hepatic increase of triacylglycerides and thiobarbituric acid-reactive substances observed after acute ethanol intoxication in rats and also causes a decrease in blood ethanol concentration. The aim of this study was to assess the effect of piroxicam on these 3 metabolic indicators, using isolated rat hepatocytes incubated with ethanol or lactate, supplemented or not with epinephrine. Epinephrine stimulated the consumption of lactate, but not of ethanol.

Hepatic and cardiac oxidative stress and other metabolic changes in broilers with the ascites syndrome.

The objective of this study was to evaluate the gluconeogenic response of in vitro stimulated hepatocytes from control broilers and broilers with clinical manifestations of the ascites syndrome. The basal rate of glucose synthesis from lactate was found to be threefold greater in sick birds than in the control group and stimulation obtained with epinephrine was found to be quantitatively similar in both groups. Under basal conditions, the hepatocytes from the sick broilers exhibited 60% more ammonium than the control birds.

Inhibition of adenosine mediated responses in isolated hepatocytes by depolarizing concentrations of K+.

Isolated rat hepatocytes, incubated in a high K+ medium which depolarizes their plasma membrane, were used to investigate the response to adenosine. High K+ concentration blocked both the adenosine mediated increase of calcium influx and the increase in the rate of urea synthesis. It is concluded that a) adenosine stimulates calcium influx in hepatocytes probably through receptor-operated Ca2+ channels which are closed by depolarization of the plasma membrane, b) the higher cytosolic calcium concentration triggers a regulatory step that fully stimulates the rate in urea synthesis.

Metabolic responses of isolated hepatocytes to adenosine; dependence on external calcium.

The role of cyclic-adenosine monophosphate (cAMP) and calcium (Ca2+) in the metabolic responses to adenosine was studied in isolated hepatocytes from fed rats. In the presence of 1.2 mM Ca but not in the absence of Ca2+, adenosine stimulated ureagenesis without increasing cAMP.

"Hormone-like" effect of adenosine and inosine on gluconeogenesis from lactate in isolated hepatocytes.

In isolated rat hepatocytes adenosine and inosine showed a dose-dependent increase in the rate of glucose synthesis from lactate with a Ka of 7.5 x 10(-8) and 9 x 10(-8) M, respectively. Absence of this action was recorded with: IMP, xanthosine, adenine, hypoxanthine, and uric acid.

Effect of adenosine and inosine on ureagenesis in hepatocytes.

Adenosine and inosine produced a dose-dependent stimulation of ureagenesis in isolated rat hepatocytes. Hypoxanthine, xanthine and uric acid were without effect. Half-maximally effective concentrations were 0.