Does acute glutamine depletion enhance the response of glutamine synthesis to fasting in muscle in adult and old rats?
OBJECTIVE
In earlier studies, skeletal muscle glutamine synthetase (GS) activity was shown to be enhanced by fasting and glucocorticoids, and inhibited by exogenous glutamine (Gln) supplementation. The current study was designed to determine whether phenylbutyrate (PhiB), a Gln-chelating agent in humans, (1) could trap Gln and produce a decline in plasma Gln in rats, as it does in humans, and (2) if so, whether (Phi)B would further enhance the response of muscle GS activity to fasting in rats.


METHODS
Adult (6-8 months) and aged (20-21 months) rats were fasted for 5 days and received two doses of 0.5 g(Phi)Bby orogastric route at times 0 and 4 h, and were then sacrificed at 5.5 h. Plasma Gln was measured by enzymatic methods, other amino acids were quantified by amino acid analysis. GS activity was measured in soleus (SO) and tibialis anterior (TA) muscles.


RESULTS
(Phi)B treatment was associated with: (1) a 20% decline in plasma Gln concentration from 572+/-54 to 424+/-34 micromol/L (P<0.05) and from 476+/-49 to 360+/-80 micromol/L (P<0.05) in fasted adult and old rats, respectively; and (2) a preservation of GS up-regulation by fasting in TA and SO muscles in both adult and aged rats, with TA muscle GS activities of 198+/-65 vs. 203+/-68 ((Phi)B-treated vs. vehicle-treated, NS), and 244+/-81 vs. 274+/-59 (NS) nmol/h/mg protein in adult and aged rats, respectively.


CONCLUSIONS
These data suggest that: (1) large doses of (Phi)B deplete plasma Gln in fasted rats, regardless of age, (2) Gln depletion induced by Phi)B does not alter GS activity.
Meynial-Denis
Dominique
D
Human Nutrition Research Center at Clermont-Ferrand, and Institut National de la Recherche Agronomique, Nutrition and Protein Metabolism Unit, Theix, 63122 Saint Genès Champanelle, France. dominique.meynial@clermont.inra.fr
Verdier
Lionel
L
Mignon
Michelle
M
Leclerc
Jean-Noël
JN
Bayle
Gérard
G
Darmaun
Dominique
D
D000367:Age Factors; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D005215:Fasting / Q000097:blood / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D005973:Glutamine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency / Q000378:metabolism* / Q000652:urine; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010654:Phenylbutyrates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002614:Chelating Agents; D010654:Phenylbutyrates; D005973:Glutamine; C003089:phenylacetylglutamine; D005974:Glutamate-Ammonia Ligase