Histamine H3 receptors in the guinea pig ileum: evidence for a postjunctional location.

The effect of the selective histamine H3 receptor agonists (R)alpha-methylhistamine, (R)MHA and immepip (IMM) on intestinal smooth muscle contractility was investigated on isolated cells from the longitudinal muscle of the guinea pig ileum. (R)MHA (10(-13)-10(-8) M) and IMM (10(-13)-10(-8) M) did not significantly modify the basal length of intestinal cells; in contrast both agonists (10(-15)-10(-11) M) prevented the contraction produced by acetylcholine (10(-7) M). The (S)-isomer of alpha-methylhistamine, (S)MHA, was inactive both on basal contractility and on acetylcholine-induced contractions. The relaxant effect of (R)MHA was not modified by famotidine (10(-7) M), but totally prevented by the selective H3 receptor antagonist clobenpropit (10(-8) M), which per se did not modify either basal contractility or the contractile response to acetylcholine. These data indicate that inhibitory histamine H3 receptors are present on smooth muscle cells of the guinea pig ileum and can be activated by very low concentrations of selective agonists. It is not clear, however, whether they can have a functional importance in the regulation of intestinal contractility in an intact system.