Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate.
The effect of inhibition of glial metabolism by infusion of fluorocitrate (FC, 1 nmol/microl, 2 microl) into the right striatum of the rat brain on the glucose metabolism was studied. Significant increases in [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake (45 min) in the right cerebral cortex and striatum were observed 4h after the infusion of FC, both as determined by the tissue dissection method and autoradiography. No significant increase in the initial uptake of [(18)F]FDG (1 min) was seen in the striatum. Pretreatment with dizocilpine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced [(18)F]FDG uptake in not only FC infused hemisphere but also in the contralateral hemisphere (saline-infused side). The radioactivity concentrations in plasma at 1, 5 and 45 min after the [(18)F]FDG injection were not altered by MK-801. This effect of MK-801 on glucose metabolism observed in the rat brain infused with FC was different from previous reports which indicated an increase in glucose metabolism in some areas of normal rat brain. In addition, the enhancement of glucose metabolism in the striatum induced by FC was almost completely abolished by pretreatment with MK-801. In the cerebral cortex, the relative ratio of radioactivity concentration in the right hemisphere to that in the left hemisphere still remained 1.37 (tissue dissection method) or 1.55 (autoradiography), which indicated that MK-801 partially blocked the effect of FC of enhancing glucose metabolism in this region. These results indicate an important role of NMDA-mediated signal transmission on the increase of glucose utilization induced by inhibition of glial metabolism.
Hirose
Shinichiro
S
Course of Allied Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. hirose@sahs.med.osaka-u.ac.jp
Umetani
Yukiko
Y
Amitani
Misato
M
Hosoi
Rie
R
Momosaki
Sotaro
S
Hatazawa
Jun
J
Gee
Antony
A
Inoue
Osamu
O
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002951:Citrates / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002951:Citrates; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D019788:Fluorodeoxyglucose F18; C007744:fluorocitrate; D005947:Glucose