Abstract

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.