Histamine H3 receptor activation inhibits sympathetic-cholinergic responses in cats

Experiments were undertaken to determine the effect of the selective histamine H3 receptor agonist (R)-alpha-methylhistamine on the amplitude of neurally evoked electrodermal (sudomotor) responses in anesthetized cats. (R)-alpha-Methylhistamine produced comparable dose-related depressions of these evoked sympathetic-cholinergic electrodermal responses elicited by either pre- or postganglionic nerve stimulation. Responses evoked by i.a. methacholine were not depressed by pretreatment with (R)-alpha-methylhistamine. (R)-alpha-Methylhistamine inhibition of preganglionic evoked responses was antagonized by pretreatment with the histamine H3 receptor antagonist thioperamide, but not by pretreatment with selective blockers of histamine H1 or histamine H2 receptors (chlorpheniramine or cimetidine). Pretreatment with thioperamide did not antagonize presynaptic inhibition produced by i.v. (-)-epinephrine, nor did rauwolscine block the inhibition produced by (R)-alpha-methylhistamine. These results suggest that (R)-alpha-methylhistamine stimulates presynaptic histamine H3 receptors located on sudomotor postganglionic nerve endings to depress neurally evoked release of acetylcholine. (R)-alpha-Methylhistamine does not appear to act at an autonomic ganglionic site in this system.