PMID- 11821150
OWN - NLM
STAT- MEDLINE
DCOM- 20020423
LR  - 20190901
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 40
IP  - 5
DP  - 2002 Apr
TI  - Alterations of purine and pyrimidine nucleotide contents in rat corticoencephalic 
      cell cultures following metabolic damage and treatment with openers and blockers 
      of ATP-sensitive potassium channels.
PG  - 427-33
AB  - Rat corticoencephalic cell cultures were investigated by high performance liquid 
      chromatography for changes in the levels of adenosine 5'-triphosphate (ATP), 
      guanosine 5'-triphosphate (GTP), uridine 5'-triphosphate (UTP), cytidine 
      5'-triphosphate (CTP), and the respective nucleoside diphosphates. Hypoxia was 
      induced by gassing the incubation medium for 30 min with 100% argon. Removal of 
      glucose was caused by washing the cultures in glucose-free medium at the 
      beginning of the 30 min incubation period. Whereas hypoxia or glucose-deficiency 
      alone failed to alter the nucleotide levels, the combination of these two 
      manipulations was clearly inhibitory. Diazoxide (300 microM) an opener of 
      ATP-dependent potassium channels (K(ATP)) did not alter the nucleotide contents 
      either in a normoxic and glucose-containing medium, or a hypoxic and glucose-free 
      medium. By contrast, the K(ATP) channel antagonist tolbutamide (300 microM) 
      aggravated the hypoxic decrease of nucleotide levels in a glucose-free medium, 
      although it was ineffective in a normoxic and glucose-containing medium. Hypoxia 
      and glucose-deficiency decreased the ATP/ADP and UTP/UDP ratios, but failed to 
      change the GTP/GDP ratio. Diazoxide and tolbutamide (300 microM each) had no 
      effect on the nucleoside triphosphate/diphosphate ratios either during normoxic 
      or during hypoxic conditions. In conclusion, corticoencephalic cultures are 
      rather resistant to in vitro ischemia. Although they clearly respond to the 
      blockade of plasmalemmal K(ATP) channels (plasmaK(ATP)) by tolbutamide, these 
      channels appear to be maximally open as a consequence of the fall in 
      intracellular nucleotides and, therefore, diazoxide has no further effect.
FAU - Reinhardt, R
AU  - Reinhardt R
AD  - Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, 
      Haertelstrasse 16-18, D-04107 Leipzig, Germany. reinr@medizin.uni-leipzig.de
FAU - Manaenko, A
AU  - Manaenko A
FAU - Pissarek, M
AU  - Pissarek M
FAU - Wagner, A
AU  - Wagner A
FAU - Illes, P
AU  - Illes P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Diphosphates)
RN  - 0 (Nucleosides)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Purine Nucleotides)
RN  - 0 (Pyrimidine Nucleotides)
RN  - 982XCM1FOI (Tolbutamide)
RN  - IY9XDZ35W2 (Glucose)
RN  - O5CB12L4FN (Diazoxide)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/*metabolism
MH  - Diazoxide/pharmacology
MH  - Diphosphates/metabolism
MH  - Embryo, Mammalian
MH  - Female
MH  - Glucose/deficiency
MH  - Nucleosides/metabolism
MH  - Potassium Channel Blockers/pharmacology
MH  - Purine Nucleotides/antagonists & inhibitors/*metabolism
MH  - Pyrimidine Nucleotides/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tolbutamide/pharmacology
EDAT- 2002/02/01 10:00
MHDA- 2002/04/24 10:01
CRDT- 2002/02/01 10:00
PHST- 2002/02/01 10:00 [pubmed]
PHST- 2002/04/24 10:01 [medline]
PHST- 2002/02/01 10:00 [entrez]
AID - S0197018601001024 [pii]
AID - 10.1016/s0197-0186(01)00102-4 [doi]
PST - ppublish
SO  - Neurochem Int. 2002 Apr;40(5):427-33. doi: 10.1016/s0197-0186(01)00102-4.