INHIBITION OF NORADRENALINE RELEASE FROM THE SYMPATHETIC-NERVES OF THE HUMAN SAPHENOUS-VEIN BY PRESYNAPTIC HISTAMINE H-3 RECEPTORS

The human saphenous vein was used to examine whether presynaptic histamine receptors can modulate noradrenaline release and, if so, to determine their pharmacological characteristics. Strips of this blood vessel were incubated with [H-3]noradrenaline and subsequently superfused with physiological salt solution containing desipramine and corticosterone. Electrically (2 Hz) evoked H-3 overflow was inhibited by histamine and the H-3 receptor agonist R-(-)-alpha-methylhistamine. Histamine-induced inhibition of electrically evoked tritium overflow was not affected by alpha-2-adrenoceptor blockade by rauwolscine. S-(+)-alpha-methylhistamine (up to 10-mu-mol/l) as well as the histamine H-1 and H-2 receptor agonists 2-(2-thiazolyl)ethylamine (up to 3-mu-mol/l) and dimaprit (up to 30-mu-mol/l), respectively, were ineffective. The selective histamine H-3 receptor antagonist thioperamide abolished the inhibitory effect of histamine. The histamine H-2 and H-1 receptor antagonists ranitidine and pheniramine, respectively, did not affect the histamine-induced inhibition of evoked tritium overflow. The present results are compatible with the suggestion that the sympathetic nerves of the human saphenous vein are endowed with inhibitory presynaptic histamine receptors of the H-3 class.