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

This study was designed to determine if the histamine H-3 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 H-3 receptor antagonist, clobenpropit (3.0 mg kg(-1), i.v.), blocked the inhibitory effect of R-alpha -methylhistamine, whereas neither the histamine H-2 receptor antagonist, cimetidine (5.0 mg kg(-1), i.v.), nor the histamine H-1 receptor antagonist, chlorpheniramine (0.5 mg kg(-1), i.v.), was effective. The histamine H-2 receptor agonist, dimaprit (10 mg kg(-1), i.v.), was also without effect on the evoked mydriasis. R-alpha -methylhistamine (3.0 mg k(-1)) did not inhibit phenylephrine-induced mydriasis. These results support the conclusion that R-alpha -methylhistamine produces inhibition of sympathetically evoked mydriasis via histamine H-3 receptor stimulation, presumably by an action on presynaptic histamine H-3 receptors. (C) 2001 Published by Elsevier Science B.V.