PMID- 10611157
OWN - NLM
STAT- MEDLINE
DCOM- 20000119
LR  - 20190707
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 118
IP  - 1
DP  - 2000 Jan
TI  - Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, 
      Raf-independent mechanism.
PG  - 90-100
AB  - BACKGROUND & AIMS: Infectious diarrhea caused by viruses plus enterotoxigenic 
      bacteria is often more severe than diarrhea induced by either pathogen alone. We 
      postulated that the increased cell adenosine 3',5'-cyclic monophosphate (cAMP) 
      concentration observed during infection by enterotoxigenic organisms retards the 
      intestinal repair process by blocking activation of mitogen-activated protein 
      kinases (MAPKs) in proliferating intestinal cells. METHODS: We evaluated the 
      effects of glutamine on MAPK activity, thymidine incorporation, and cell number 
      in glutamine-starved and -sufficient rat intestinal crypt cells (IEC-6). RESULTS: 
      In glutamine-starved cells, 10 mmol/L glutamine in the absence of serum 
      stimulated [(3)H]thymidine incorporation 8-fold. This effect was inhibited by 60% 
      with 8-(4-chlorophenylthio) (8-CPT)-cAMP (100 micromol/L) + isobutyl 
      methylxanthine (100 micromol/L). In cells not starved of glutamine, glutamine 
      stimulated thymidine incorporation by 3-fold, and 8-CPT-cAMP completely blocked 
      the mitogenic effect. Inhibition of proliferation by cAMP persisted for at least 
      68 hours after cAMP removal. In vitro kinase assays showed that glutamine 
      signaling requires an intact ERK (extracellular signal-related kinase) pathway in 
      unstarved cells. In starved cells, at least one other pathway (JNK) was activated 
      by glutamine, and the mitogenic inhibition by 8-CPT-cAMP was incomplete. Other 
      intestinal fuels (glucose and acetate) were not mitogenic. CONCLUSIONS: Increased 
      levels of intracellular cAMP inhibit ERKs but only partially reduce 
      glutamine-stimulated proliferation in enterocytes adapted to low glutamine.
FAU - Rhoads, J M
AU  - Rhoads JM
AD  - Department of Pediatrics, University of North Carolina, Chapel Hill, 
      NC27599-7220, USA.
FAU - Argenzio, R A
AU  - Argenzio RA
FAU - Chen, W
AU  - Chen W
FAU - Graves, L M
AU  - Graves LM
FAU - Licato, L L
AU  - Licato LL
FAU - Blikslager, A T
AU  - Blikslager AT
FAU - Smith, J
AU  - Smith J
FAU - Gatzy, J
AU  - Gatzy J
FAU - Brenner, D A
AU  - Brenner DA
LA  - eng
GR  - DK 34987/DK/NIDDK NIH HHS/United States
GR  - R01-GM-51905/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Thionucleotides)
RN  - 0RH81L854J (Glutamine)
RN  - 41941-66-6 (8-((4-chlorophenyl)thio)cyclic-3',5'-AMP)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 9007-49-2 (DNA)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Cyclic AMP/analogs & derivatives/*metabolism/pharmacology
MH  - DNA/biosynthesis/drug effects
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/metabolism/pharmacology
MH  - Flavonoids/pharmacology
MH  - Glutamine/*metabolism/pharmacology
MH  - Intestinal Mucosa/*metabolism
MH  - Intestines/cytology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Oxygen Consumption/drug effects
MH  - Thionucleotides/pharmacology
MH  - Thymidine/metabolism
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - S0016508500616128 [pii]
AID - 10.1016/s0016-5085(00)70417-3 [doi]
PST - ppublish
SO  - Gastroenterology. 2000 Jan;118(1):90-100. doi: 10.1016/s0016-5085(00)70417-3.