Adenosine A1 receptors mediate chronic ethanol-induced increases in receptor-stimulated cyclic AMP in cultured hepatocytes

Nagy, Laura E.; DeSilva, S E F

doi:10.1042/bj3040205

Cited by 21 publications

(16 citation statements)

References 32 publications

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“…The doses of the A1R ligands used were not lethal, but they are expected to cause transient hemodynamic, cardiac, and thermogenic alterations [64], which were not measured, and can indirectly affect the measured impact of I/R on the liver. However, although we did not directly ruled out the possible involvement of other adenosine receptors in the liver or indirectly affecting liver function, we favor the contention that the effects observed upon administration of A1R ligands mostly result from direct effects mediated by liver A1R [30], since preconditioning studies in different organs in vivo and in vitro agreed on a direct effect of A1R in the affected cells [27,[31][32][33]. Since ATP content declines substantially during I/R, which is associated with hepatocellular injury and higher mortality, prevention of defective energy production plays an important role in the resistance to I/R injury.…”

Section: Discussionmentioning

confidence: 59%

“…Accumulated evidence suggests that A1R play a role in the protection from I/R injury in several organs such as heart, brain, and lung [12][13][14][26][27][28][29][30][31][32][33][34][35][36][37] through mechanisms that remain to be defined. The present study suggests that A1R activation prevents I/R injury through the control of OXPHOS efficiency.…”

Section: Discussionmentioning

confidence: 99%

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Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Duarte

Amorim

Varela

et al. 2016

Purinergic Signalling

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Although adenosine A 1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N 6 -cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% warm ischemia and 16 h of reperfusion (I/R), and the IPC group underwent a 5-min ischemic episode followed by a 10-min period of reperfusion before I/R. DPCPX or CCPA was administered intraperitoneally 2 h before IPC or I/R. The control of mitochondrial function emerged as the central element affected by IPC and controlled by endogenous A1R activation. Thus, livers from IPC-or CCPA-treated rats displayed an improved oxidative phosphorylation with higher state 3 respiratory rate, higher respiratory control ratio, increased ATP content, and decreased lag phase. IPC and CCPA also prevented the I/Rinduced susceptibility to calcium-induced mitochondrial permeability transition, the rate of reactive oxygen species (ROS) generation, and the decreased mitochondrial content of phospho-Ser 9 GSK-3β. DPCPX abrogated these effects of IPC. These implicate the control of GSK-3β activity by Aktmediated Ser 9 -GSK-3β phosphorylation preserving the efficiency of oxidative phosphorylation and ROS-mediated cell death in the ability of A1R activation to mimic IPC in the liver. In conclusion, the parallel between IPC and A1R-mediated preconditioning also paves the way to consider a putative therapeutic use of the later in liver transplants.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Duarte

Amorim

Varela

et al. 2016

Purinergic Signalling

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“…Hepatocytes were isolated from male C57BL/6 mice, as previously described ( 33 ), and suspended in William's E Medium with 10% FBS and primary hepatocyte supplement pack (Gibco, Grand Island, NY). Hepatocytes were then plated and cultured at a density of ‫ف‬ 95,000 cells/well in a collagen-coated 24-well plate.…”

Section: Hdl Binding and Uptake Assays By Primary Mouse Hepatocytesmentioning

confidence: 99%

HDL from apoA1 transgenic mice expressing the 4WF isoform is resistant to oxidative loss of function

Berisha

Brubaker

Kasumov

et al. 2015

Journal of Lipid Research

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High levels of high density lipoprotein-cholesterol (HDL-C) are associated with lower risk for cardiovascular disease in epidemiological studies ( 1 ). Although several mechanisms may play a role in HDL's protective effect, HDL and its major protein constituent, apoA1, are critical components of the reverse cholesterol transport (RCT) pathway, in which cholesterol is removed from peripheral tissues and transferred to the liver for excretion. In the fi rst step of the RCT pathway, lipid-poor apoA1 acts as an acceptor for cell cholesterol and phospholipids via the cell membrane protein ABCA1, generating nascent HDL.Recently, "HDL is the good cholesterol" hypothesis has suffered several setbacks. For example, several trials of HDL-C-raising drugs, including cholesteryl ester transfer protein inhibitors and niacin, failed to demonstrate clinical benefi t ( 2-5 ). Furthermore, a Mendelian randomization study did not associate gene variants that solely alter HDL-C with coronary artery disease (CAD) incidence ( 6 ). That said, human and mouse models with defective RCT, via mutations in ABCA1, apoA1, or scavenger receptor class B type I (SR-BI), are more susceptible to atherosclerosis independent Abstract HDL functions are impaired by myeloperoxidase (MPO), which selectively targets and oxidizes human apoA1. We previously found that the 4WF isoform of human apoA1, in which the four tryptophan residues are substituted with phenylalanine, is resistant to MPO-mediated loss of function. The purpose of this study was to generate 4WF apoA1 transgenic mice and compare functional properties of the 4WF and wild-type human apoA1 isoforms in vivo . Male mice had signifi cantly higher plasma apoA1 levels than females for both isoforms of human apoA1, attributed to different production rates. With matched plasma apoA1 levels, 4WF transgenics had a trend for slightly less HDL-cholesterol versus human apoA1 transgenics. While 4WF transgenics had 31% less reverse cholesterol transport (RCT) to the plasma compartment, equivalent RCT to the liver and feces was observed. Plasma from both strains had similar ability to accept cholesterol and facilitate ex vivo cholesterol effl ux from macrophages. Furthermore, we observed that 4WF transgenic HDL was partially ( ‫ف‬ 50%) protected from MPOmediated loss of function while human apoA1 transgenic HDL lost all ABCA1-dependent cholesterol acceptor activity. In conclusion, the structure and function of HDL from 4WF transgenic mice was not different than HDL derived from human apoA1 transgenic mice. -Berisha, S.

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“…Striatal A2AR signaling Striatal adenosine levels play an important role in ethanol sensitivity, withdrawal, and drinking (Arolfo et al, 2004;Gordon and Diamond, 1993;Meng and Dar, 1995;Nagy and DeSilva, 1994). The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, while A1Rs are widely distributed throughout the CNS.…”

Section: Adenosine Receptor Signaling In Ethanol Drinkingmentioning

confidence: 99%

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

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Adenosine A1 receptors mediate chronic ethanol-induced increases in receptor-stimulated cyclic AMP in cultured hepatocytes

Cited by 21 publications

References 32 publications

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

HDL from apoA1 transgenic mice expressing the 4WF isoform is resistant to oxidative loss of function

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

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