Histamine H-3 receptors in the guinea pig ileum: Evidence for a postjunctional location

The effect of the selective histamine H-3 receptor agonists (R)alpha-methyl histamine, (R)MHA and immepip (IMM) on intestinal smooth muscle contractili ty was investigated on isolated cells from the longitudinal muscle of the g uinea pig ileum. (R)MHA (10(-13)-10(-8) M) and IMM (10(-13)-10(-8) M) did n ot significantly modify the basal length of intestinal cells; in contrast b oth agonists (10(-15)-10(-11) M) prevented the contraction produced by acet ylcholine (10(-7) M). The (S)-isomer of alpha-methylhistamine, (S)MHA, was inactive both on basal contractility and on acetylcholine-induced contracti ons. The relaxant effect of (R)MHA was not modified by famotidine (10(-7) M ), but totally prevented by the selective H-3 receptor antagonist clobenpro pit (10(-8) M), which per se did not modify either basal contractility or t he contractile response to acetylcholine. These data indicate that inhibito ry histamine H-3 receptors are present on smooth muscle cells of the guinea pig ileum and can be activated by Very low concentrations of selective ago nists. It is not clear, however, whether they can have a functional importa nce in the regulation of intestinal contractility in an intact system. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medicales Elsevier SAS.