Effect of glutamatergic systems on in vivo binding of [(125)I]beta-CIT in the brain of a rat model of Parkinson's disease.
The effect of MK-801, a noncompetitive NMDA receptor antagonist, on both in vivo and in vitro binding of [(125)I]beta-CIT (RTI-55) was investigated in a rat model of Parkinson's disease. The binding experiments were performed 2 weeks after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA). In the in vitro binding study, no alterations in [(125)I]beta-CIT binding in rat brain sections were observed after addition of MK-801, 0.03 microM or 3 microM, to the incubation medium. However, in vivo [(125)I]beta-CIT binding to the dopamine transporter in both nonlesioned and 6-OHDA-lesioned striatum was significantly increased by pretreatment with MK-801. In vivo [(125)I]beta-CIT binding to the serotonin (5HT) transporter in nonlesioned cerebral cortex, hypothalamus, and thalamus was also significantly increased by MK-801. However, the degree of change in the specific binding of [(125)I]beta-CIT induced by MK-801 was smaller in the lesioned cerebral cortex. Kinetic analysis, by a simplified three-compartment model with the cerebellum as the reference region, revealed that these alterations in the in vivo [(125)I]beta-CIT binding induced by MK-801 were mainly due to changes in the rate constants of in vivo binding, the input rate constant, k(3), and the output rate constant, k(4). These results indicate that the glutamatergic system significantly affects the function of dopamine transporters in the degenerated dopaminergic neurons in Parkinson's disease.
Kagawa
Shinya
S
Division of Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. kagawa@tracer.med.osaka-u.ac.jp
Nakano
Takayuki
T
Inoue
Osamu
O
Nishimura
Tsunehiko
T
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology; D013565:Sympatholytics
D018691:Excitatory Amino Acid Antagonists; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013565:Sympatholytics; D012701:Serotonin; D018698:Glutamic Acid; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D003042:Cocaine; D004298:Dopamine