The role of histamine H-1, H-2 and H-3 receptors on enteric ascending synaptic transmission in the guinea pig ileum

The role of histamine H-1-, H-2- and H-3-receptors was studied on neural tr ansmission in ascending excitatory pathways of the guinea pig ileum. A two- compartment (oral and anal compartments) bath was used: ascending neural pa thways were activated by electrical stimulation in the anal compartment and the resulting contraction of the circular muscle in the oral compartment w as recorded. Drugs were applied in the anal compartment and each agonist wa s evaluated in the presence of the antagonists of the other two receptors. In the presence of cimetidine (10 mu M) and thioperamide (1 mu M), histamin e (0.03-3 mu M) depressed the nerve-mediated contractions (5-70% inhibition , P <.05-.01). The inhibitory effect of histamine was antagonized by mepyra mine. At the higher concentrations (10 and 30 mu M), histamine elicited con tractions of the circular muscle in the oral compartment, and these were ab olished by mepyramine (1 mu M) and tetrodotoxin (0.6 mu M). The H-2 agonist s dimaprit (30 and 100 mu M) and amphamine (0.1-300 mu M) produced small co ntractions of the circular muscle in the oral compartment. These contractil e responses were abolished by tetrodotoxin (0.6 mu M) and cimetidine (10 mu M). The H-3 agonist R-alpha-methylhistamine (0.001-1 mu M) inhibited (2-58 %, P <.05) the nerve-mediated contractions. This inhibitory effect was anta gonized by the H-3 antagonist thioperamide. These results indicate that 1) histamine, acting at H-1 receptors, at lower concentrations depresses synap tic transmission, although at higher concentrations activates the enteric e xcitatory ascending pathway; 2) activation of H-2 receptors by H-2 agonists stimulates the enteric excitatory ascending pathways and 3) activation of H-3 receptors inhibits synaptic transmission.