Histamine H3 receptor activation inhibits sympathetic-cholinergic responses in cats

Abstract Experiments were undertaken to determine the effect of the selective histamine H 3 receptor agonist ( R )- α -methylhistamine on the amplitude of neurally evoked electrodermal (sudomotor) responses in anesthetized cats. ( R )- α -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 )- α -methylhistamine. ( R )- α -Methylhistamine inhibition of preganglionic evoked responses was antagonized by pretreatment with the histamine H 3 receptor antagonist thioperamide, but not by pretreatment with selective blockers of histamine H 1 or histamine H 2 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 )- α -methylhistamine. These results suggest that ( R )- α -methylhistamine stimulates presynaptic histamine H 3 receptors located on sudomotor postganglionic nerve endings to depress neurally evoked release of acetylcholine. ( R )- α -Methylhistamine does not appear to act at an autonomic ganglionic site in this system.