Histamine H3 receptor-mediated inhibition of endogenous acetylcholine release from the isolated, vascularly perfused rat stomach

We studied the effects of histamine H-3 receptor ligands on the release of endogenous acetylcholine from the isolated, vascularly perfused rat stomach. The stomach was perfused via the celiac artery with modified Krebs-Ringer solution containing physostigmine. Released acetylcholine from the portal vein was electrochemically measured using high-performance liquid chromatography and an enzyme system. Vagus nerves were electrically stimulated twice for 2 min (0.5 or 2.5 Hz). Acetylcholine release evoked at 2.5 Hz was slightly inhibited by histamine and effectively potentiated by thioperamide, a histamine H-3 receptor antagonist. Acetylcholine release evoked at 0.5 Hz in the presence of atropine was not influenced by thioperamide, but effectively inhibited by histamine, R-alpha-methylhistamine or imetit, histamine H-3, receptor agonists. These inhibitory effects were abolished by thioperamide or pertussis toxin. These results suggest that histamine attenuates acetylcholine release from vagus nerves through histamine H-3 receptor-mediated and pertussis toxin-sensitive mechanisms in the rat stomach. (C) 2000 Elsevier Science B.V. All rights reserved.