The effect of dopamine D1 receptor stimulation on the up-regulation of histamine H3-receptors following destruction of the ascending dopaminergic neurones

Jong Hoon Ryu, Kazuhiko Yanai, Xiao Lan Zhao, Takehiko Watanabe

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

1. The binding of [3H]-(R)α-methylhistamine and [3H]-N(α)-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)α-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 D1-receptors in the substantia nigra was markedly decreased after administration of 6-hydroxydopamine. 5. The treatment with (S)α-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)-α-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.

Original languageEnglish
Pages (from-to)585-592
Number of pages8
JournalBritish Journal of Pharmacology
Volume118
Issue number3
DOIs
Publication statusPublished - 1996

Keywords

  • (S)-α-fluoromethylhistidine
  • 6-hydroxydopamine
  • Denervation
  • Dopamine D-receptors
  • Dopamine D-receptors
  • Histamine H-receptor
  • Quinpirole
  • SKF38393
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Pharmacology

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