TY - JOUR
T1 - Ethanol Alters the Metabolic Response of Isolated, Perfused Rat Liver to a Phagocytic Stimulus
AU - D'Souza, Nympha B.
AU - Bagby, Gregory J.
AU - Lang, Charles H.
AU - Deaciuc, Ion V.
AU - Spitzer, John J.
PY - 1993/2
Y1 - 1993/2
N2 - Intercellular communication in the liver is a potentially important mechanism for the regulation of hepatic metabolism. Since alcohol (ethanol, ETOH) can interact with both parenchymal and nonparenchymal cells, the present study was performed to assess the possible effects of ETOH on the nonparenchymal cell‐to‐hepatocyte signal traffic by studying the glycogenolytic and glycolytic response of the perfused rat liver to colloidal carbon, a phagocytic stimulus for Kupffer and sinusoidal endothelial cells. Livers from fed rats were perfused with hemoglobin‐free Krebs Ringer bicarbonate buffer containing ETOH (20 mm) or acetaldehyde (1 mm). Twenty minutes after initiating the infusion of ETOH or acetaldehyde, colloidal carbon was infused and the rate of carbon uptake, glucose, lactate and pyruvate output, and oxygen consumption were determined. In control livers, carbon stimulated the output of glucose (60%), lactate (25%), and pyruvate (53%), without affecting the lactate/pyruvate ratio. ETOH, but not acetaldehyde, enhanced the carbon effect on glucose output (38%), but suppressed the increased lactate and pyruvate output (48% and 91% respectively) resulting in a dramatic 10‐fold increase in the lactate/pyruvate ratio. By using inhibitors of cyclooxygenase or alcohol dehydrogenase (indomethacin and 4‐methylpyrazole, respectively) in the presence of carbon and/or ETOH, we determined that: (1) following carbon stimulation prostaglandins are the likely mediators secreted by nonparenchymal cells that increase carbohydrate output; and (2) the ETOH‐induced enhancement of carbonstimulated glycogenolysis is also mediated by prostaglandins and is not dependent on the oxidative metabolism of ETOH.
AB - Intercellular communication in the liver is a potentially important mechanism for the regulation of hepatic metabolism. Since alcohol (ethanol, ETOH) can interact with both parenchymal and nonparenchymal cells, the present study was performed to assess the possible effects of ETOH on the nonparenchymal cell‐to‐hepatocyte signal traffic by studying the glycogenolytic and glycolytic response of the perfused rat liver to colloidal carbon, a phagocytic stimulus for Kupffer and sinusoidal endothelial cells. Livers from fed rats were perfused with hemoglobin‐free Krebs Ringer bicarbonate buffer containing ETOH (20 mm) or acetaldehyde (1 mm). Twenty minutes after initiating the infusion of ETOH or acetaldehyde, colloidal carbon was infused and the rate of carbon uptake, glucose, lactate and pyruvate output, and oxygen consumption were determined. In control livers, carbon stimulated the output of glucose (60%), lactate (25%), and pyruvate (53%), without affecting the lactate/pyruvate ratio. ETOH, but not acetaldehyde, enhanced the carbon effect on glucose output (38%), but suppressed the increased lactate and pyruvate output (48% and 91% respectively) resulting in a dramatic 10‐fold increase in the lactate/pyruvate ratio. By using inhibitors of cyclooxygenase or alcohol dehydrogenase (indomethacin and 4‐methylpyrazole, respectively) in the presence of carbon and/or ETOH, we determined that: (1) following carbon stimulation prostaglandins are the likely mediators secreted by nonparenchymal cells that increase carbohydrate output; and (2) the ETOH‐induced enhancement of carbonstimulated glycogenolysis is also mediated by prostaglandins and is not dependent on the oxidative metabolism of ETOH.
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U2 - 10.1111/j.1530-0277.1993.tb00740.x
DO - 10.1111/j.1530-0277.1993.tb00740.x
M3 - Article
C2 - 8452196
AN - SCOPUS:0027447937
SN - 0145-6008
VL - 17
SP - 147
EP - 154
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 1
ER -