PT - JOURNAL ARTICLE AU - Angelo A. Izzo AU - Marcello Costa AU - Nicola Mascolo AU - Francesco Capasso TI - The Role of Histamine H<sub>1</sub>, H<sub>2</sub> and H<sub>3</sub> Receptors on Enteric Ascending Synaptic Transmission in the Guinea Pig Ileum DP - 1998 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 952--957 VI - 287 IP - 3 4099 - http://jpet.aspetjournals.org/content/287/3/952.short 4100 - http://jpet.aspetjournals.org/content/287/3/952.full SO - J Pharmacol Exp Ther1998 Dec 01; 287 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 &lt;.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 &lt;.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