The effect of dopamine D1 receptor stimulation on the up-regulation of histamine H3-receptors following destruction of the ascending dopaminergic neurones.
1. The binding of [3H]-(R)alpha-methylhistamine and [3H]-N alpha-methylhistamine to histamine H3-receptors, [3H]-SCH23390 to dopamine D1-receptors, and [3H]-YM09151-2 to dopamine D2-receptors was investigated by quantitative receptor autoradiography in the rat brain following 6-hydroxydopamine injection into the substantia nigra. 2. The levels of [3H]-(R)alpha-methylhistamine binding sites in the denervated striatum and substantia nigra were significantly higher than those in the contralateral side from 1 week to 12 weeks after nigral lesions. The H3-receptor binding was maximal at 3 weeks after nigral lesions and maintained until 12 weeks. 3. The increased number of histamine H3-receptors was decreased to the level of the contralateral side by chronic treatment with a selective dopamine D1 agonist, SKF38393, but not modified by a selective dopamine D2 agonist, quinpirole. 4. Dopamine D1- and D2-receptors in the striatum were similarly up-regulated after unilateral nigral lesion. On the other hand, the number of dopamine D2-receptors in the substantia nigra was markedly decreased after administration of 6-hydroxydopamine. 5. The treatment with (S)alpha-fluoromethylhistidine increased the H3-receptor binding in both the ipsilateral and contralateral sides. As a result, the magnitude of the ratio of the H3-receptor binding between ipsilateral and contralateral sides was partially attenuated by treatment with (S)-alpha-fluoromethylhistidine. 6. These results strongly suggest that the expression of histamine H3-receptors in the striatum and substantia nigra is influenced through D1-receptors by tonic nigrostriatal dopaminergic inputs.
Ryu
J H
JH
Department of Pharmacology I, Tohoku University School of Medicine, Sendai, Japan.
Yanai
K
K
Zhao
X L
XL
Watanabe
T
T
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation
D001552:Benzazepines; D018100:Receptors, Histamine H3; D016627:Oxidopamine; D004298:Dopamine