The functional role of neuronal histamine H3 receptors in acid process was investigated using immepip analog VUF5810 and the non-imidazole compound FUB649, a selective H3-receptor antagonist.The H3/H4-receptor ligands immepip and THIO were studied for comparison.The effects of different drugs on elec. field stimulation (EFS) or exogenous pentagastrin (PGAS)-induced acid secretion were studied.VUF5810 (30-100 μM) significantly inhibited EFS-induced hypersecretion (maximal reduction being 42.98± 5.62%), while leaving unaltered the response to PGAS.Conversely, the mixed H3/H4 agonist immepip (30 μM) was ineffective against either stimuli.THIO (1μM) or FUB 649 (1μM) alone did not modify EFS-induced secretion, but prevented the inhibitory effect of VUF5810.Thus, the use of highly selective H3-receptor ligands allowed identification of inhibitory H3 receptors in the peripheral cholinergic neurons of rat gastric mucosa.The lack of effect of VUF5810 on PGAS-induced acid secretion could be explained by the occurrence of inhibitory H3 receptors on D cells and inhibitory H3 receptors on enterochromaffin-like cells with opposite effects on acid secretion.Finally, the ineffectiveness of the H3/H4 agonist immepip would suggest H4-receptor-mediated excitatory effects.
