Levodopoa but not bromocriptine induces AP-1 and creb DNA-binding activity in the dopamine-depleted striatum of the rat.
To elucidate the neurochemical mechanism that underlies the effect of anti-parkinsonian agents on motor activities in the dopamine-depleted striatum, we evaluated AP-I and CREB DNA-binding activity in the striatum of 6-hydroxydopamine-lesioned rats by use of a gel mobility-shift assay. Rats with a unilateral lesion of the nigrostriatal dopamine pathway were injected i.p. with either SKF38393 (a DI receptor agonist), bromocriptine (a D2 receptor agonist), or levodopa (a Dl/D2 receptor agonist). Each treatment increased the number of rotational responses of rats contralateral to the lesioned side. However, only SKF38393 and levodopa increased AP-I and CREB DNA-binding activity in the dopamine-depleted striatum. As with the expression of c-fos, supersensitive DI receptors may play a key role in the enhanced induction of AP-I and CREB DNA-binding activity in the dopamine-depleted striatum. Supershift analysis revealed that c-Fos; and Jun family proteins are the main components for AP-1 induced in the dopamine-depleted striaturn by SKF38393 or levodopa.
Kashihara
K
K
Department of Neurology, Okayama University Medical School, Japan.
Akiyama
K
K
Ishihara
T
T
Shiro
Y
Y
Shohmori
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D010302:Parkinson Disease, Secondary / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*
D000978:Antiparkinson Agents; D017362:Cyclic AMP Response Element-Binding Protein; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D018808:Transcription Factor AP-1; D001971:Bromocriptine; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine