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

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.

• Authors: Y Yu, M Kawarai, M C Koss
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 419 Issue 1 Pg. 55-9 (May 04 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11348630 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Histamine Agonists
• Histamine Antagonists
• Histamine H1 Antagonists
• Histamine H2 Antagonists
• Imidazoles
• Methylhistamines
• Chlorpheniramine
• alpha-methylhistamine
• Cimetidine
• Thiourea
• clobenpropit
• Dimaprit

Topics

• Animals
• Chlorpheniramine (pharmacology)
• Cimetidine (pharmacology)
• Dimaprit (pharmacology)
• Dose-Response Relationship, Drug
• Electric Stimulation
• Histamine Agonists (pharmacology)
• Histamine Antagonists (pharmacology)
• Histamine H1 Antagonists (pharmacology)
• Histamine H2 Antagonists (pharmacology)
• Imidazoles (pharmacology)
• Male
• Methylhistamines (pharmacology)
• Mydriasis (physiopathology)
• Pupil (physiology)
• Rats
• Rats, Sprague-Dawley
• Sympathetic Nervous System (drug effects, physiology)
• Thiourea (analogs & derivatives, pharmacology)