Histamine H3 receptor-mediated inhibition of sympathetically evoked mydriasis in rats

Y Yu, M Kawarai, M C Koss

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

This study was designed to determine if the histamine H3 receptor agonist R-alpha-methylhistamine would play a role in modulation of sympathetically evoked mydriasis in anesthetized rats, and if so, to ascertain the specific receptor subtype(s) involved. Reproducible frequency-response curves of pupillary dilation were generated by stimulation of the cervical preganglionic sympathetic nerve (1-32 Hz). Systemic administration of R-alpha-methylhistamine (0.3-3.0 mg kg(-1)) produced a dose-related inhibition of the evoked mydriasis. The greatest inhibition was seen at lower frequency levels, with about 43% depression observed at 2 Hz. The specific histamine H3 receptor antagonist, clobenpropit (3.0 mg kg(-1), i.v.), blocked the inhibitory effect of R-alpha-methylhistamine, whereas neither the histamine H2 receptor antagonist, cimetidine (5.0 mg kg(-1), i.v.), nor the histamine H1 receptor antagonist, chlorpheniramine (0.5 mg kg(-1), i.v.), was effective. The histamine H2 receptor agonist, dimaprit (10 mg kg(-1), i.v.), was also without effect on the evoked mydriasis. R-alpha-methylhistamine (3.0 mg kg(-1)) did not inhibit phenylephrine-induced mydriasis. These results support the conclusion that R-alpha-methylhistamine produces inhibition of sympathetically evoked mydriasis via histamine H3 receptor stimulation, presumably by an action on presynaptic histamine H3 receptors.
Original languageEnglish
Pages (from-to)55-9
Number of pages5
JournalEuropean Journal of Pharmacology
Volume419
Issue number1
Publication statusPublished - 04 May 2001

Keywords

  • Animals
  • Chlorpheniramine
  • Cimetidine
  • Dimaprit
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Histamine Agonists
  • Histamine Antagonists
  • Histamine H1 Antagonists
  • Histamine H2 Antagonists
  • Imidazoles
  • Male
  • Methylhistamines
  • Mydriasis
  • Pupil
  • Rats
  • Rats, Sprague-Dawley
  • Sympathetic Nervous System
  • Thiourea

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