Substitutes for glutamine in proliferation of rat intestinal epithelial cells.
OBJECTIVE
Glutamine (Gln) is important for intestinal epithelial proliferation. The purpose of this study was to determine whether glutamate (Glu), a mixture of nucleotide monophosphates, arginine, or glucosamine could support proliferation of rat intestinal crypt cells (IEC-6) in the absence of Gln.


METHODS
Glu with added ammonia acetate, glucosamine, arginine, and nucleotide monophosphates were tested at concentrations that were isonitrogenous with respect to Gln. To determine whether de novo synthesis of Gln was affected by these nutrients, a duplicate set of treatment groups was also tested with 1.0 mM/L of methionine sulfoximine, an inhibitor of Gln synthetase.


RESULTS
Gln + methionine sulfoximine-treated cells showed suboptimal proliferation below 0.6 mM/L but normal proliferation between 0.6 and 4.0 mM/L of Gln. In the absence of exogenous Gln, isonitrogenous concentrations of Glu, glucosamine, arginine, or nucleotide monophosphates yielded similar proliferation as Gln. Cells treated with Glu, glucosamine, arginine, or nucleotide monophosphate mixture showed a decrease in proliferation compared with cells treated with Gln across all treatment doses (P < 0.03).


CONCLUSIONS
The importance of these results is that, in the presence of active Gln synthetase, these nutrients can maintain intestinal epithelial proliferation similar to that observed with Gln.
Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA.
Lauren M
LM
Tuhacek
Amy D
AD
Mackey
Nan
N
Li
Vincent G
VG
DeMarco
Gary
G
Stevens
Josef
J
Neu
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005944:Glucosamine / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D018698:Glutamic Acid / Q000494:pharmacology; D005973:Glutamine / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D000085:Acetates; D005973:Glutamine; D018698:Glutamic Acid; D001120:Arginine; D005974:Glutamate-Ammonia Ligase; D005944:Glucosamine; C018824:ammonium acetate