PRESYNAPTIC HISTAMINE H-2, RECEPTORS MODULATE THE SYMPATHETIC-NERVE TRANSMISSION IN THE ISOLATED RAT VAS-DEFERENS - NO ROLE FOR H-3 RECEPTORS

The modulatory activity mediated by histamine receptors on the sympath etic nerve transmission was investigated in the rat vas deferens. Agon ists and antagonists acting at the different histamine receptor subtyp es (H-1, H-2 and H-3) were tested on electrically-driven preparations in vitro. Low-frequency stimulation (0.1 Hz) evoked muscle contraction s almost completely-sustained by A;TP release, while at high-frequency stimulation (5-10 Hz) norepinephrine was mainly involved. The H-1 rec eptor agonists, pyridilethylamine and 2-(2 aminoethyl)thiazole, enhanc ed the electrically evoked twitch responses, but not contractions indu ced by exogenously-applied norepinephrine and ATP. These effects were prevented by the H-1-blocking drugs, mepyramine and phenyramine, but o nly at high concentrations (10 mu mol/l). All these H-1-antagonists st rongly enhanced muscle response to electrical stimulation. The H-2 rec eptor agonists, dimaprit, amthamine and impromidine, reduced the contr actions evoked by field stimulation, but not by exogenously applied no repinephrine and ATP, the effect being antagonised by H-2-blocking dru gs, ranitidine and famotidine. The H-3 receptor agonist, R(alpha)-meth ylhistamine, reduced the electrically evoked muscle contractions, the effect being not modified by the selective H-3-blocking drug, thiopera mide, but prevented by famotidine. These data suggest that rat vas def erens contains presynaptic histamine H-2 receptors, able to mediate in hibitory effects on the sympathetic transmission, while histamine H-3 receptors are apparently not involved. On the contrary, the role of H- 1 is still unclear, since both agonists and antagonists may have the s ame effects.