Long-lasting binding of IT-066 to human histamine H2 receptor.
Hiroko OtsukaYasushi FukushimaMichiko TamaiHaruki TakahashiHaruki MoriTomoichiro AsanoTakao KatsubeKenji OgawaTetsuro KajiwaraSin-ichiro OhkawaToshihito Saitoh
6
Citation
19
Reference
10
Related Paper
Citation Trend
Keywords:
Famotidine
Thioperamide
Dimaprit
Paraformaldehyde
Cimetidine
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 microM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 microM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 microM 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 microM 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.
Dimaprit
Thioperamide
Mepyramine
Cimetidine
Cite
Citations (17)
Thioperamide
Dimaprit
Histaminergic
Mepyramine
Cimetidine
Cite
Citations (0)
Thioperamide
Dimaprit
Histaminergic
Mepyramine
Cimetidine
Cite
Citations (0)
Histamine plays an important role in the control of gastric acid secretion by activating H2 receptors located on parietal cells. In gastric mucosa, histamine is stored both in mast cells and in enterochromaffin-like cells, especially in rodents. It has been proposed that histamine may regulate its own synthesis and/or release through receptors pharmacologically distinct from H1- and H2-receptor subtypes. In this article, we studied the regulation by histamine of histidine decarboxylase (HDC) activity (enzyme responsible for the formation of histamine by decarboxylation of L-histidine) in a fraction of isolated rabbit gastric mucosal cells enriched in mucous and endocrine cells. Histamine and (R)-alpha-methylhistamine (H3 receptor agonist) dose dependently inhibited HDC activity with the same potency (mean effective concn: 32.2 +/- 0.7 and 50.5 +/- 3.1 pM, respectively) and efficacy (35 and 36% inhibition, respectively). In contrast, the H2 agonist dimaprit was devoid of effect. The H3 antagonist thioperamide was found to decrease the histamine- or (R)-alpha-methylhistamine-induced inhibition of HDC activity (mean ineffective concn = 28.3 +/- 1.8 and 9.87 +/- 0.8 nM, respectively), whereas H1 (promethazine) and H2 (ranitidine) antagonists were unable to affect HDC activity. Moreover, high concentrations of thioperamide (1-10 microns) increased histamine release from these cells. All these results allowed us to conclude that, in gastric mucosa, histamine downregulates its own synthesis (and perhaps release) through the stimulation of autoreceptors with pharmacological characteristics of H3 receptors. However, the relationship between histamine synthesis and release remains unclear and needs further investigation.
Dimaprit
Thioperamide
Histidine decarboxylase
Histamine H4 receptor
Histamine N-methyltransferase
Enterochromaffin-like cell
Cite
Citations (32)
Anaphylactic histamine release from isolated rat peritoneal mast cells was concentration-dependently blocked by a 5-min treatment with exogenous histamine at 0.9 and 9 μM and enhanced by a 20- to 30-min treatment with thioperamide (H3-antagonist) at 3 μΜ. with significance, but little affected by mepyramine (H1-antagonist) and cimetidine (H2-antagonist) at the cell concentration of 106 mast cells/ml. At a low concentration of mast cells (104 mast cells/ml), (R)-α-methylhistamine (α-MH), an H3-agonist, at 0.9-90 μΜ also inhibited the release in a concentration-dependent fashion. Thioperamide, but neither mepyramine nor cimetidine, significantly restored the decreased release by α-MH. However, the complete restoration by thioperamide could not be achieved because the drug itself slightly but concentration-dependently inhibited anaphylactic histamine release. On the other hand, not only betahistine and dimaprit but also α-MH did not suppress histamine release from the mast cells induced by compound 48/80. In rat plasma, considerable levels of histamine were detected. From these results, it is strongly suggested that histamine H3-like receptors are largely responsible for the negative feedback regulation of the anaphylactic histamine release from rat peritoneal mast cells.
Mast (botany)
Histamine H4 receptor
Cite
Citations (27)
Thioperamide
Dimaprit
Histaminergic
Mepyramine
Cimetidine
Cite
Citations (7)
Effects of substances that are able to alter the histamine level, a histamine H1-receptor agonist and antagonist, and a histamine H2-receptor agonist were investigated in an anxiety-like state in mice by means of the light/dark box test. Diazepam was used as positive control. The histamine H3-receptor antagonist, thioperamide (2, 5, and 20 mg/kg sc), showed an anxiogenic-like effect that reached a maximum with the dosage of 5 mg/kg. The histamine-N-methyltransferase (HMT) inhibitor, metoprine (5 and 20 mg/kg sc), also decreased the time in the light at the highest dose used and, likewise, the highly selective histamine H1-receptor agonist, 2-(3-trifluoromethylphenyl)histamine (FMPH) (2.65 and 6.5 μg/mouse, icv). On the contrary, the histamine H2-receptor agonist, impromidine (3, 10, 20, and 30 μg/mouse, icv), dose-dependently showed an anxiolytic-like effect. The selective histamine H1 antagonist, pyrilamine (20 mg/kg ip) was able to prevent the anxiogenic-like effect of FMPH significantly, and that of thioperamide partially, while the effect caused by metoprine remained unvaried. It is suggested that the histaminergic system modulates anxiety-like states via the activation of both postsynaptic receptors in a contrasting manner: activation of the H1 receptor causes an anxiogenic-like effect, while that of the H2 receptors reduces anxiousness. However, on the basis of effects observed with the substances capable of releasing endogenous histamine, it seems likely that the anxiogenic-like effect is prevalent.
Thioperamide
Anxiogenic
Histaminergic
Dimaprit
Cite
Citations (2)
Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.1-1.0 mu g) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H1-antagonists (diphenhydramine and chlorpheniramine) but also H2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-alpha-methylhistamine, a selective H3 agonist. In addition, the effect induced by thioperamide was inhibited by H1 and H2 antagonists, indicating that the H3 receptor also participates in histamine-induced hypothermia.
Thioperamide
Dimaprit
Cimetidine
Mepyramine
Cite
Citations (17)
Thioperamide
Histaminergic
Anxiogenic
Dimaprit
Histamine H4 receptor
Histamine N-methyltransferase
Cite
Citations (64)
Thioperamide
Enterochromaffin cell
Dimaprit
Histaminergic
Cite
Citations (45)