The mechanism of adenosine release from hypoxic rat liver cells

Belloni, Francis L.; Elkin, Peter L.; Giannotto, Beverly

doi:10.1111/j.1476-5381.1985.tb08880.x

Cited by 40 publications

(14 citation statements)

References 21 publications

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“…Endogenous adenosine may play a role in the conversion of the normally proabsorptive gut to its observed prosecretory status during short-term ischemic stress. During both chemical and true hypoxia, adenosine has been shown to accumulate in the extracellular space and to exert local regulatory effects in several non-intestinal tissues and cell types, including kidney and isolated renal tubules, hepatocytes, cardiac muscle, brain, and erythrocytes (12,16,17,30,33,34,43,44,50 (38). Epithelial Cl-secretion is thought to represent a primitive defense mechanism whereby mucosal surfaces can be "flushed" in response to potentially injurious stimuli (39,49).…”

Section: Discussionmentioning

confidence: 99%

Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers.

Matthews

Tally²,

Smith³

et al. 1995

J. Clin. Invest.

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Intestinal ischemia is characterized by rapid early inhibition of absorptive function and the appearance of net secretion, although why active secretion persists in the setting of a mucosal energy deficit is unknown. The cryptlike epithelial line T84, a well-characterized model of intestinal Cl -secretion, develops a prominent increase in short-circuit current (I,, indicative of active Cl-transport) in response to "hypoxia" induced by metabolic inhibitors. The increased L is associated with the initial decrease in monolayer ATP content. The LC is transient and disappears with progressive energy depletion, although graded degrees of ATP depletion induce a more sustained L response. Chromatographic analysis and secretory bioassays show that the IS response to metabolic inhibitors is related to the endogenous release of adenosine into the extracellular space in quantities sufficient to interact locally with stimulatory adenosine receptors. Unlike its classical role as a metabolic feedback inhibitor, adenosine appears to function as an autocrine "feedforward" activator of active intestinal Cl -secretion. These studies suggest a novel role for adenosine in the conversion of the gut from an absorptive to a secretory organ during ischemic stress, thus contributing to the initial diarrheal manifestations of intestinal ischemia. (J. Clin. Invest. 1995. 96:117-125.)

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Section: Discussionmentioning

confidence: 99%

Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers.

Matthews

Tally²,

Smith³

et al. 1995

J. Clin. Invest.

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“…AMP is catabolized by AMP deaminase to inosine monophosphate in the inosine pathway, which would circumvent the production of adenosine. [21254255261] AMP deaminase in rat brain extracts, however, is inhibited at ischemic ATP concentrations resulting in AMP breakdown to adenosine almost exclusively through the adenosine pathway. [18] Further, extracellular ATP is exclusively metabolized to adenosine by ecto-5’ nucleotidase.…”

Section: Relative Hepatic Hypoxia In Metabolic Syndromementioning

confidence: 99%

Metabolic syndrome and the hepatorenal reflex

Wider¹

2016

Surg Neurol Int

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Insufficient hepatic O2 in animal and human studies has been shown to elicit a hepatorenal reflex in response to increased hepatic adenosine, resulting in the stimulation of renal as well as muscle sympathetic nerve activity and activating the renin angiotensin system. Low hepatic ATP, hyperuricemia, and hepatic lipid accumulation reported in metabolic syndrome (MetS) patients may reflect insufficient hepatic O2 delivery, potentially accounting for the sympathetic overdrive associated with MetS. This theoretical concept is supported by experimental results in animals fed a high fructose diet to induce MetS. Hepatic fructose metabolism rapidly consumes ATP resulting in increased adenosine production and hyperuricemia as well as elevated renin release and sympathetic activity. This review makes the case for the hepatorenal reflex causing sympathetic overdrive and metabolic syndrome in response to exaggerated splanchnic oxygen consumption from excessive eating. This is strongly reinforced by the fact that MetS is cured in a matter of days in a significant percentage of patients by diet, bariatric surgery, or endoluminal sleeve, all of which would decrease splanchnic oxygen demand by limiting nutrient contact with the mucosa and reducing the nutrient load due to loss of appetite or dietary restriction.

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“…That effect might at least partially be responsible for the higher PVR in livers preserved in SAPs and PPSs for the following reason: during hepatic ischemia [3], hepatocytes or other parenchymal cells [2] are thought to release adenosine into the perivascular space, where it binds to A2-adenosine receptors and reduces the vasculotonus [ 121. When interstitial adenosine concentrations are increased by inhibiting adenosine deamination, hepatic reperfusion and graft function is improved [20].…”

Section: Discussionmentioning

confidence: 99%

Anionic polysaccharides. A class of substances with hepatoprotective and antiadhesive properties in rat liver preservation

et al. 2002

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In liver preservation, the substitution of the anion C1-by lactobionic acid (LB) prevents reperfusion edema and extends the preservation time for human livers. We studied the effect of compounds that are structurally related to lactobionic acid: anionic polycarbohydrates (sulfated anionic polysaccharide, SAP, and pentosan polysulfate, PPS) on liver function and leukocyte-endothelid cell interaction in isolated perfusion and liver transplant models. Rat livers, coldstored (24 h) in a C1--containing control solution, became edematous during 1 h of reperfusion. Substitution of C1-by either LB, SAP, or PPS decreased reperfusion edema in a C1-concentration-dependent fashion. Reperfusion edema was abolished completely after preservation in 100 mM SAP solution or PPS solution. Also hepatic lactic dehydrogenase (LDH) and aspartate aminotransferase (ASAT) release was lowest after preservation in those solutions. After preservation in LB or anionic polycarbohydrate solutions, portal venous resistance was significantly higher than after preservation in Cl--containing control solution.

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The mechanism of adenosine release from hypoxic rat liver cells

Cited by 40 publications

References 21 publications

Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers.

Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers.

Metabolic syndrome and the hepatorenal reflex

Anionic polysaccharides. A class of substances with hepatoprotective and antiadhesive properties in rat liver preservation

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