Sequential changes of [H]forskolin, [H]cyclohexyladenosine and [H]PN200-110 binding sites in the brain of 6-hydroxydopamine-lesioned rats.
Receptor autoradiographic technique was studied to investigate sequential changes in adenylyl cyclase, adenosine A1 receptors and L-type calcium channels in the striatum and substantia nigra 1-8 weeks after unilateral 6-hydroxydopamine injection of the medial forebrain bundle in rats. [3H]Forskolin, [3H]cyclohexyladenosine (CHA) and [3H]PN200-110 were used to label adenylyl cyclase, adenosine A1 receptors and L-type calcium channels, respectively. The degeneration of the nigrostriatal pathway caused a significant increase in [3H]forskolin binding in the striatum of both the ipsilateral and contralateral sides from 2 to 4 weeks post-lesion. The ipsilateral substantia nigra showed a transient increase in [3H]forskolin binding 4 weeks post-lesion. In contrast, [3H]CHA binding showed no significant change in most brain areas after lesioning. On the other hand, a conspicuous decrease in [3H]PN200-110 binding was observed in the dorsolateral striatum of ipsilateral side 4 weeks post-lesion. Thereafter, the striatum of both the ipsilateral and contralateral sides showed a significant decrease in [3H]PN200-110 binding 8 weeks post-lesion. These results demonstrate that unilateral 6-hydroxydopamine into the medial forebrain bundle of rats can experimentally cause a significant increase in adenylyl cyclase binding sites in the striatum and substantia nigra, whereas no conspicuous change in adenosine A1 receptors is observed in these areas during post-lesion. In contrast, L-type calcium channels were progressively damaged in the striatum after unilateral 6-hydroxydopamine treatment. These findings suggest that adenylyl cyclase and calcium system may contribute to the degeneration processes of the dopaminergic neurones.
Araki
T
T
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Tanji
H
H
Kato
H
H
Imai
Y
Y
Mizugaki
M
M
Itoyama
Y
Y
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001923:Brain Chemistry / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000032:analysis / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism; D017275:Isradipine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000737:chemistry / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism*; D016627:Oxidopamine; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000378:metabolism; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism; D013565:Sympatholytics; D014316:Tritium
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018340:Receptors, Adrenergic, alpha-1; D013565:Sympatholytics; D014316:Tritium; D005576:Colforsin; C027513:N(6)-cyclohexyladenosine; D016627:Oxidopamine; D000241:Adenosine; D017275:Isradipine