Summary
Frequency-dependent pupillary dilations were evoked by electrical stimulation of the pre- or post-ganglionic cervical sympathetic nerve (sympatho-excitation) or the hypothalamus (parasympatho-inhibition) in sympathectomized anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist (R)-α-methylhistamine (RαMeHA) produced a dose-dependent depression of mydriasis due to direct neural sympathetic activation but had no effect on responses elicited by parasympathetic withdrawal. The histamine H2 receptor agonist, dimaprit, was inactive. RαMeHA was much more effective in depressing sympathetic responses obtained at lower frequencies when compared to higher frequencies of stimulation.
Responses evoked both pre- and postganglionically were inhibited by RαMeHA. This peripheral sympathoinhibitory action of RαMeHA was antagonized by the histamine H3 receptor blocker thioperamide but not by intravenous pretreatment with the histamine H1 receptor antagonist chlorpheniramine. Histamine H2 receptor blockers cimetidine and ranitidine were also without effect. RαMeHA did not depress pupillary responses elicited by i.v. (-)-adrenaline.
The results demonstrate that histamine H3 receptors modulate sympathetic activation of the iris at a site proximal to the iris dilator muscle. The predominant mechanism of action appears to the prejunctional inhibition of noradrenaline release from postganglionic sympathetic nerve endings. However, a concomitant ganglionic inhibitory action cannot be excluded.
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Correspondence to M. C. Koss at the above address
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Koss, M.C., Hey, J.A. Prejunctional inhibition of sympathetically evoked pupillary dilation in cats by activation of histamine H3 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 348, 141–145 (1993). https://doi.org/10.1007/BF00164790
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DOI: https://doi.org/10.1007/BF00164790