Abstract
The role of histamine H3-receptors in the control of acetylcholine release from peripheral cholinergic neurons was evaluated in the isolated guinea pig ileum, previously loaded with 3H-choline. When tested in the presence of H1- and H2-blockade, histamine (0.1-100 mumol/l) and (R) alpha-methylhistamine (0.01-1 mumol/l) dose-dependently reduced the electrically-evoked choline outflow, with (R) alpha-methylhistamine being a partial agonist. Selective H3-receptor blocking drugs, thioperamide (0.1 mumol/l) and impromidine (0.1 mumol/l) reversed the histamine-induced inhibitory effect. These data suggest that intestinal cholinergic nerves are endowed with histamine H3-receptors whose activation produces an inhibitory effect upon acetylcholine release. The practical implications of these findings are obvious.
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