Dopamine metabolism in the striatum of hemiparkinsonian model rats with dopaminergic grafts.
To investigate dopamine (DA) levels as well as DA metabolism by which the striatal DAergic grafts may bring the functional recovery to hemiparkinsonian model rats, a microdialysis study was performed in the striatum, and an autoradiographic analysis for DA transporter was made. In hemiparkinsonian model rats, the concentrations of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatal perfusates, decreased considerably (less than 5%, of control levels). In grafted rats that showed motor recovery, the concentration of DA recovered to almost control level, and DOPAC and HVA to about 20% of controls' suggesting that the rate of DA metabolism is low. L-DOPA loading to grafted rats induced a big release of DOPAC and HVA, thus the DOPAC/DA ratio was close to that of the controls'. Methamphetamine loading increased the concentration of DA but did not change the level of DOPAC and HVA. Haloperidol loading increased DA, DOPAC and HVA. [3H]mazindol binding that reflects the activity of the DA transporter decreased considerably in hemiparkinsonian model rats, but it reappeared more or less in grafted rats. Data indicated that in grafted striatum, the extracellular DA level is almost normal level while the rate of DA metabolism is low. By L-DOPA loading, the grafts show the capacity to synthesize, release and metabolize DA and then the DOPAC/DA ratio is normalized. Responses to methamphetamine and haloperidol, as well as the results of the autoradiographic study suggest that the grafts are under a good feedback regulation of DA metabolism.
Hashitani
T
T
Department of Physiology, Nagoya City University Medical School, Nagoya, Japan.
Mizukawa
K
K
Kumazaki
M
M
Nishino
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D016332:Fetal Tissue Transplantation; D007839:Functional Laterality; D006220:Haloperidol / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D008454:Mazindol / Q000378:metabolism; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000502:physiology / Q000637:transplantation*; D008694:Methamphetamine / Q000494:pharmacology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D014316:Tritium; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D007980:Levodopa; D016627:Oxidopamine; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D004298:Dopamine; D006719:Homovanillic Acid