Dimaprit, a Histamine H₂-Agonist, Inhibits Anaphylactic Histamine Release from Mast Cells and the Decreased Release Is Restored by Thioperamide (H₃-Antagonist), but Not by Cimetidine (H₂-Antagonist)

Abstract

Whether anaphylactic histamine release from rat peritoneal mast cells is influenced by betahistine, a histamine H₁-receptor agonist/H₃-antagonist, and dimaprit, an H₂-agonist, was examined. Treatment with dimaprit at 6 and 60 μM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 μM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 μM for 1 to 20 min and for 5 to 20 min, respectively, caused a time-dependent inhibition of the release, but up to 30 min treatment with 8 and 80 μM betahistine had no effect. The decreased histamine release induced by dimaprit was recovered by neither mepyramine nor cimetidine. However, thioperamide, an H₃-selective antagonist, dose-dependently restored the diminished release. From these results, the inhibition of anaphylactic histamine release by dimaprit is not produced by the stimulation of H₂-receptors, but involves the stimulation of H₃-like receptors or H₃-subtype receptors, which are distinct from the H₃-receptors located in brain, and suggests that the receptor plays an important role in the negative feedback regulation of histamine release.