Vol. 287, Issue 3, 952-957, December 1998

The Role of Histamine H₁, H₂ and H₃ Receptors on Enteric Ascending Synaptic Transmission in the Guinea Pig Ileum¹

Angelo A. Izzo, Marcello Costa, Nicola Mascolo and Francesco Capasso

Department of Experimental Pharmacology (A.A.I., N.M., F.C.), University of Naples "Federico II" via D. Montesano 49, 80131 Naples, Italy and Department of Human Physiology and Centre for Neuroscience (M.C.), School of Medicine, The Flinders University of South Australia, GPO Box 2100, Adelaide 5001, SA, Australia

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 H₃ agonist R--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 H₂ agonists stimulates the enteric excitatory ascending pathways and 3) activation of H₃ receptors inhibits synaptic transmission.