RT Journal Article SR Electronic T1 The Role of Histamine H1, H2 and H3 Receptors on Enteric Ascending Synaptic Transmission in the Guinea Pig Ileum JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 952 OP 957 VO 287 IS 3 A1 Angelo A. Izzo A1 Marcello Costa A1 Nicola Mascolo A1 Francesco Capasso YR 1998 UL http://jpet.aspetjournals.org/content/287/3/952.abstract AB The role of histamine H1-, H2- and H3-receptors was studied on neural transmission in ascending excitatory pathways of the guinea pig ileum. A two-compartment (oral and anal compartments) bath was used: ascending neural pathways were activated by electrical stimulation in the anal compartment and the resulting contraction of the circular muscle in the oral compartment was recorded. Drugs were applied in the anal compartment and each agonist was evaluated in the presence of the antagonists of the other two receptors. In the presence of cimetidine (10 μM) and thioperamide (1 μM), histamine (0.03–3 μM) depressed the nerve-mediated contractions (5–70% inhibition, P <.05–.01). The inhibitory effect of histamine was antagonized by mepyramine. At the higher concentrations (10 and 30 μM), histamine elicited contractions of the circular muscle in the oral compartment, and these were abolished by mepyramine (1 μM) and tetrodotoxin (0.6 μM). The H2 agonists dimaprit (30 and 100 μM) and amphamine (0.1–300 μM) produced small contractions of the circular muscle in the oral compartment. These contractile responses were abolished by tetrodotoxin (0.6 μM) and cimetidine (10 μM). The H3agonist R-α-methylhistamine (0.001–1 μM) inhibited (2–58%, P <.05) the nerve-mediated contractions. This inhibitory effect was antagonized by the H3 antagonist thioperamide. These results indicate that 1) histamine, acting at H1 receptors, at lower concentrations depresses synaptic transmission, although at higher concentrations activates the enteric excitatory ascending pathway; 2) activation of H2 receptors by H2agonists stimulates the enteric excitatory ascending pathways and 3) activation of H3 receptors inhibits synaptic transmission. The American Society for Pharmacology and Experimental Therapeutics