scholarly journals α-adrenergic stimulation of glutamine metabolism in isolated rat hepatocytes

1985 ◽  
Vol 230 (2) ◽  
pp. 457-463 ◽  
Author(s):  
A J Verhoeven ◽  
J M Estrela ◽  
A J Meijer

The mechanisms by means of which phenylephrine stimulates glutamine metabolism were studied in isolated rat hepatocytes. In the first 2 min after phenylephrine addition there was a rapid fall in the concentrations of intracellular 2-oxoglutarate and glutamate, presumably owing to activation of 2-oxoglutarate dehydrogenase. This was followed 2-3 min later by activation of glutaminase and by increases in glutamate and 2-oxoglutarate. Activation of glutaminase by phenylephrine was due to direct stimulation of the enzyme rather than to reversal of inhibition by the decrease in 2-oxoglutarate and glutamate. The stimulation of glutaminase by phenylephrine is partly due to an increase in the affinity of the enzyme for ammonia, its essential activator. It is concluded that stimulation of steady-state flux through the pathway from glutamine to glucose and urea can only be achieved by stimulation of glutaminase, the first enzyme in the pathway.

FEBS Letters ◽  
1980 ◽  
Vol 120 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Mary C. Sugden ◽  
Ann F.C. Tordoff ◽  
Vera Ilic ◽  
Dermont H. Williamson

1983 ◽  
Vol 210 (3) ◽  
pp. 867-873 ◽  
Author(s):  
A Binet ◽  
M Claret

1. The alpha-adrenergic agonists noradrenaline (in the presence of beta-blocker) and phenylephrine cause a transient stimulation of the respiration in isolated rat hepatocytes. After a lag period of 12s, this activation first attains its maximal value (+24%) for about 1 min and then falls to a sustained value (+15%). The effect is blocked by the alpha-antagonists phenoxybenzamine and phentolamine. It is dose-dependent, with an half-maximal stimulation by 16 nM-noradrenaline, which is similar to that found for other cell responses to the hormone. 2. Vasopressin and ATP, which in common with alpha-agonists are believed to increase intracellular [Ca2+], induce similar activation in the respiration rate. 3. The alpha-adrenergic-mediated respiration depends on extracellular Ca2+. The activation is decreased or abolished when extracellular [Ca2+] is decreased by adding EGTA, or when the Ca2+ antagonists Mn2+ and La3+ are present in the incubation medium. 4. It is suggested that the activation of the mitochondrial respiration rate results from the increase in cytosolic Ca2+ concentration, presumably via Ca2+ influx or Ca2+ release from the plasma membrane or endoplasmic reticulum.


1987 ◽  
Vol 246 (2) ◽  
pp. 449-454 ◽  
Author(s):  
A Lavoinne ◽  
H A Buc ◽  
S Claeyssens ◽  
M Pinosa ◽  
F Matray

Incubation of hepatocytes from 24 h-starved rats in the presence of 0.5 mM-adenosine decreased gluconeogenesis from lactate, but not from alanine. The inhibition of gluconeogenesis was associated with a stimulation of ketone-body production and an inhibition of pyruvate oxidation. These metabolic changes were suppressed in the presence of iodotubercidin (an inhibitor of adenosine kinase), but were reinforced in the presence of deoxycoformycin (an inhibitor of adenosine deaminase); 2-chloroadenosine induced no change in gluconeogenesis from lactate. These data indicate that the inhibition of gluconeogenesis by adenosine probably results from its conversion into adenine nucleotides. In the presence of lactate or pyruvate, but not with alanine or asparagine, this conversion resulted in a decrease in the [ATP]/[ADP] ratio in both mitochondrial and cytosolic compartments. Adenosine decreased the Pi concentration with all gluconeogenic substrates.


1987 ◽  
Vol 245 (2) ◽  
pp. 371-374 ◽  
Author(s):  
R Guinzberg P ◽  
I Laguna ◽  
A Zentella ◽  
R Guzman ◽  
E Piña

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 0.08 microM for adenosine and 5 microM for inosine. Activation of ureagenesis by both nucleosides had the following characteristics: (a) it was observed with either glutamine or (NH4)2CO3, provided that glucose was present; (b) it was not detected when glucose was replaced by lactate plus oleate; (c) it was mutually antagonized by glucagon, but not by adrenaline; and (d) it was dependent on Ca2+. We suggest that the action of adenosine and inosine on ureagenesis might be of physiological significance.


1993 ◽  
Vol 246 (2) ◽  
pp. 113-120 ◽  
Author(s):  
Takahide Nomura ◽  
Haruhito Kondo ◽  
Seiko Hasegawa ◽  
Toshiko Watanabe ◽  
Rie Yokoyama ◽  
...  

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