PK11195 might selectively suppress the quinolinic acid-induced enhancement of anaerobic glycolysis in glial cells.
PK11195 was previously reported to attenuate the quinolinic acid (QUIN)-induced enhancement of glucose metabolism in rat brain. In the present study, the effect of PK11195 or anesthesia on [(14)C]2-deoxyglucose ([(14)C]DG) uptake was investigated in order to determine whether the QUIN-induced enhancement of glucose metabolism occurred in glial cells or neurons. We confirmed that the microinjection of QUIN caused a significant enhancement of [(14)C]DG uptake at 2h after the infusion, while the co-injection of PK11195 and QUIN almost completely suppressed this enhancement of [(14)C]DG uptake. No effect of chloral hydrate anesthesia on the QUIN-induced enhancement of [(14)C]DG uptake was observed. In contrast to rats treated with QUIN, PK11195 did not affect the enhancement of [(14)C]DG uptake induced by fluorocitrate (FC); however, chloral hydrate anesthesia completely suppressed the FC-induced increase in [(14)C]DG uptake. These results indicated that the enhancement of glucose metabolism induced by QUIN mainly occurred in glial cells, and the neuroprotective effect of PK11195 in rats injected with QUIN might be related to the suppression of anaerobic glycolysis in glial cells.
Momosaki
Sotaro
S
Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan. momosaki@sahs.med.osaka-u.ac.jp
Imamoto
Natsumi
N
Hosoi
Rie
R
Sawada
Yoshikazu
Y
Abe
Kohji
K
Zhang
Ming-Rong
MR
Inoue
Osamu
O
D000693:Anaerobiosis / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D007546:Isoquinolines; D018696:Neuroprotective Agents; D017378:Quinolinic Acid; D005947:Glucose; C037850:PK 11195