Involvement of β-Adrenergic Systems in the Antagonizing Effect of Paeoniflorin on the Scopolamine-Induced Deficit in Radial Maze Performance in Rats

Abstract

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 uM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 pM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 pM for 1 to 20 min and for 5 to 20 min, respectively, caused a time-dependent inhibi tion of the release, but up to 30 min treatment with 8 and 80 pM 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 H2receptors, 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 feed back regulation of histamine release.

Possible Participation of Histamine H3-Receptors in the Regulation of Anaphylactic Histamine Release from Isolated Rat Peritoneal Mast Cells

“…Taking this report into consideration together with our previous report (26) on the inhibition of anaphylactic histamine release by dimaprit described above and the relatively high concen trations of a-MH necessary to inhibit the release in the present results, it is suggested that H3-receptors on the rat peritoneal mast cell are a subtype distinct from those in the rat brain.…”

“…Besides the present results that a-MH decreased the anaphylactic histamine release from isolated rat mast cells, we have recently found that dimaprit (H2-agonist) (22) at relatively high concentrations of 0.6 to 60 pM also concentration-dependently decreased the release, which was restored by the coexistence of thioperamide, but not by mepyramine and cimetidine, while betahistine [H, agonist (23)/H3-antagonist (24,25)] does not influence the anaphylactic histamine release (26). On the other hand, as shown in the present results, dimaprit and a-MH as well as betahistine trivially influenced compound 48/80-induced histamine release.…”

Human basophil chemotaxis and activation are regulated via the histamine H4 receptor

“…Thioperamide is now described as a selective H3/4R antagonist . As the H4R was not yet discovered at the time of their observation, the authors concluded that H3R‐like receptors were responsible for the negative feedback regulation of histamine . Based on our current findings that indeed, the H4R plays a role in FcεRI‐dependent processes by inhibiting basophil activation and degranulation, we can assume that the suppressive effect on the histamine release in their study was at least in part attributable to the H4R.…”

“…In contrast to the study with human leukocytes , the H2R antagonist cimetidine did not affect the decreased release of histamine from rat peritoneal mast cells. Interestingly, the reduced release could be dose dependently restored by thioperamide . Thioperamide is now described as a selective H3/4R antagonist .…”

“…Several immunologic effects of histamine during basophil or mast cell activation in both in vitro assays and in the course of allergen immunotherapy were described in the literature . Former studies provided evidence that histamine is able to inhibit its own release in human leukocytes or mast cells . It was shown in one of these early studies that histamine and different H2R agonists inhibit the histamine release from human leukocytes with high potency.…”