Histamine H3 receptor-mediated inhibition of sympathetically evoked mydriasis in rats.
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.
Yu
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Department of Cell Biology, University of Oklahoma College of Medicine, PO Box 26901, Oklahoma City, OK 73190, USA.
Kawarai
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Koss
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D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D015878:Mydriasis / Q000503:physiopathology*; D011680:Pupil / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D002744:Chlorpheniramine; C069357:alpha-methylhistamine; D002927:Cimetidine; D013890:Thiourea; C086108:clobenpropit; D017259:Dimaprit