Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; Brain Diseases ; enzymology ; metabolism ; Disease Models, Animal ; Histamine ; metabolism ; Humans ; Membrane Proteins ; metabolism ; Receptors, Histamine ; metabolism ; Receptors, Leukotriene ; metabolism

OBJECTIVETo identify a HEK293 cell line containing stably-transfected H3R gene, and to screen the novel non-imidazole compounds with H3R antagonist activity.

METHODSThe expression of rat H3 receptor in cell line was detected by RT-PCR and Western blot. An elevation of intercellular cAMP concentration induced by forskolin was measured as the index for screening compounds with H3R antagonist activity.

RESULTSThe H3R-transfected HEK-293 cells stably expressed high level of rat H3 receptor mRNA and protein. Forskolin significantly increased intercellular cAMP concentration in the H3R-transfected HEK-293 cells. H3R agonist (R)-α-methylhistamine inhibited the forskolin-induced production of intercellular cAMP. H3R antagonist thioperamide and newly synthesized non-imidazole compounds XHA23 and XHA25 blocked (R)-α- methylhistamine reversal of forskolin-induced cAMP formation in a concentration-dependent manner, and the IC50 values were 3.62 μmol/L, 0.49 μmol/L, 0.14 μmol/L, respectively.

CONCLUSIONThe H3R-transfected HEK293 cells stably express high level of rat H3 receptor, and can be used for screening compounds with H3R antagonist activity. The non-imidazole compounds XHA23 and XHA25 may have H3R antagonist activity.

Animals ; Drug Evaluation, Preclinical ; HEK293 Cells ; Histamine H3 Antagonists ; Humans ; Rats ; Receptors, Histamine H3 ; genetics ; metabolism ; Transfection

OBJECTIVE: To observe expression and distribution of histamine H4 receptor in nasal mucosa in normal people and allergic rhinitis patients,and understand role of histamine H4 receptor in allergic rhinitis. METHOD: Select normal people and allergic rhinitis patients each 10, take the nasal mucosa, detect expression and distribution of histamine H4 receptor at proteins and transcription level respectively by immunohistochemical method and RT-PCR, and compared. RESULT: Histamine H4 receptor at proteins and transcription level were found in normal nasal mucosa (25 509 +/- 6 441, 0.42 +/- 0.08), increased significantly in nasal mucosa of allergic rhinitis patients (49 676 +/- 8 541, 0.69 +/- 0.11, P < 0.05), which in structural cells and immune cells. CONCLUSION Histamine H4 receptors exist in normal nasal mucosa, its express significantly enhance, flew histamine H4 receptor may be mediated histamine in pathogenesis of allergic rhinitis ,who is one of the ligands of histamine.
Case-Control Studies ; Humans ; Nasal Mucosa ; immunology ; metabolism ; pathology ; Receptors, G-Protein-Coupled ; metabolism ; Receptors, Histamine ; metabolism ; Receptors, Histamine H4 ; Rhinitis, Allergic, Perennial ; immunology ; metabolism ; pathology

OBJECTIVETo investigate the influence of substance P (SP) on the release of histamine in the human hypertrophic scar tissue, and to explore the prerequisite of their interaction.

METHODSTissue specimens of normal skin and hypertrophic scar from eight hospitalized patients were excised and cut into 0.5 to 1.0 mm3 pieces, and the histamine release by mast cell (MC) under the stimulation of different concentration of SP and calcium, as well as the different affect time of SP, were determined with fluorescence spectrometer. Then the histamine release rate was calculated.

RESULTSThere was obvious release of histamine when SP concentration was 1 x 10(-6) mol/L , and the release rate was (50.0 +/- 3.6) %, which was significantly higher than that by SP in the concentration of 0 mol/L [(44.0 +/- 3.2) %, P < 0.01]. Therefore it seemed to be dose-dependent. About 90% of histamine was released within 15 minutes of 5 x 10(-1) mol/L Substance P stimulation, and it was also time-dependent. The histamine release reached the peak when calcium concentration was 5 x 10(-3) mol/L, which seemed to be dose-dependent, but it decreased transiently when calcium concentration was 1 x 10(-3) mol/L. In all occasions, the influence of SP on the histamine release by MC in hypertrophic scar (HS) was markedly higher than that in normal skin (NS) (P < 0.01). Conclusion The influence of SP on the histamine release by MC in HS was markedly higher than that in NS, and it might be closely related to itching sensation and the formation of hypertrophic scar.

Child ; Child, Preschool ; Cicatrix, Hypertrophic ; metabolism ; Female ; Histamine ; metabolism ; Humans ; Male ; Skin ; metabolism ; Substance P ; pharmacology

AIMTo investigate the effect of selective H3 receptor agonist(R)-alpha-methylhistamine and antagonist thioperamide on the respiratory response in asthmatic guinea pigs respectively.

METHODSAnesthesized guinea pigs were prepared with a implanted intracerebroventricular (icv) cannula and instrumented for the measurement of respiratory rate (RR) and diaphragmatic electric activity (DA). Substance P-like immunoreactive (SP-LI) substances in lower respiratory tract were detected by immunohistochemical method. Brain histamine contents were measured by fluorometric determination.

RESULTS(1) Intravenous injection of ovalbumin caused tachypnea and significant decrease in DA magnitude. At the same time, SP-LI substances increased in trachea, bronchus and lung. (2) Administration of selective H3 receptor agonist (R)-alpha-methylhistamine (5 microg) icv immediately after i.v. ovalbumin could significantly ameliorate the changes in RR and DA induced by ovalbumin. In accordance, SP-LI substances in lower respiratory tract markedly decreased at 5 min and 10 min after (R)-alpha-methylhistamine microinjection. (3) Icv thioperamide (20 microg) caused a significant increase in RR and a decrease in DA. (4) Brain histamine contents increased in hypothalamus and cortex during asthma. After microinjection of thioperamide (20 microg) icv significant increase of histamine contents in hypothalamus and cortex was observed.

CONCLUSIONBrain histamine H3 receptors may be related to asthmatic respiratory responses.

Animals ; Asthma ; metabolism ; Brain ; metabolism ; Guinea Pigs ; Histamine Agonists ; pharmacology ; Histamine H3 Antagonists ; pharmacology ; Lateral Ventricles ; Male ; Methylhistamines ; pharmacology ; Muscle Contraction ; Piperidines ; pharmacology ; Receptors, Histamine H3 ; metabolism ; Substance P ; metabolism ; Trachea ; physiopathology

Spinal α-motoneurons directly innervate skeletal muscles and function as the final common path for movement and behavior. The processes that determine the excitability of motoneurons are critical for the execution of motor behavior. In fact, it has been noted that spinal motoneurons receive various neuromodulatory inputs, especially monoaminergic one. However, the roles of histamine and hypothalamic histaminergic innervation on spinal motoneurons and the underlying ionic mechanisms are still largely unknown. In the present study, by using the method of intracellular recording on rat spinal slices, we found that activation of either H or H receptor potentiated repetitive firing behavior and increased the excitability of spinal α-motoneurons. Both of blockage of K channels and activation of Na-Ca exchangers were involved in the H receptor-mediated excitation on spinal motoneurons, whereas the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels were responsible for the H receptor-mediated excitation. The results suggest that, through switching functional status of ion channels and exchangers coupled to histamine receptors, histamine effectively biases the excitability of the spinal α-motoneurons. In this way, the hypothalamospinal histaminergic innervation may directly modulate final motor outputs and actively regulate spinal motor reflexes and motor execution.
Animals ; Histamine ; pharmacology ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; metabolism ; Motor Neurons ; drug effects ; physiology ; Rats ; Receptors, Histamine H2 ; metabolism ; Sodium-Calcium Exchanger ; metabolism

OBJECTIVETo investigate the effects of histamine on the neurotoxicity induced by beta-amyloid(1-42)(Abeta42) in rat phaeochromocytoma (PC12) cells.

METHODSThe in vitro model of Alzheimer's disease was constructed with A beta42-treated PC12 cells. Cell morphology and MTT assay were used to evaluate the cell toxicity and histamine effects. The different histamine antagonists were applied to investigate the involvement of receptor subtypes.

RESULTThe neurotoxicity was induced by A beta42 in a concentration-dependent manner, which was reversed by histamine at concentration of 10(-7), 10(-6) mol/L. The effect was reversed by H(2) antagonist zolantidine and H(3)antagonist clobenpropit, but not by H(1) antagonist diphenhydramine.

CONCLUSIONHistamine reduces neurotoxicity induced by beta-amyloid(1-42), which may be mediated by H(2) and H(3)receptors.

Alzheimer Disease ; chemically induced ; metabolism ; prevention & control ; Amyloid beta-Peptides ; toxicity ; Animals ; Benzothiazoles ; pharmacology ; Diphenhydramine ; pharmacology ; Dose-Response Relationship, Drug ; Histamine ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histamine H3 Antagonists ; pharmacology ; Imidazoles ; pharmacology ; Neuroprotective Agents ; metabolism ; pharmacology ; PC12 Cells ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Rats ; Receptors, Histamine H2 ; metabolism ; Receptors, Histamine H3 ; metabolism ; Thiourea ; analogs & derivatives ; pharmacology

Determining positive food challenges are not easy as there is an absence of simple and objective tests. Histamine, an essential mediator for allergic reactions, is involved in the pathogenesis of atopic dermatitis (AD) and food challenges can change histamine levels. The significances of a prick test with histamine (histamine prick test, HPT) relating to the interpretation of food challenges in AD were evaluated. A total of 467 AD patients participated in this study. Skin prick tests, identification of specific IgE and open food challenge were conducted for the identification of food allergy. Elimination diet was performed with HPT. HPTs were conducted before and after food challenges. The wheal sizes by HPT were significantly decreased after an elimination diet. The relative changes of wheal sizes significantly correlated with those of clinical severity scores in AD patients (p<0.001). The wheal sizes in HPT were increased with a positive provocation in open food challenges. In conclusion, HPT may be a simple and objective test to interprete the results of food challenges in patients with AD. The exact mechanisms of the changes in skin reactivity by HPT need further investigation.
Child ; Dermatitis, Atopic/immunology/*metabolism ; Food ; Histamine/*metabolism ; Human ; Skin Tests

OBJECTIVETo investigate histamine-induced changes of the intracortical vessels in the cortical slice of rat brain.

METHODSImmunohistochemistry was employed to detect the expression of H1 and H2 receptors in the intracortical blood vessels of rats. Histamine-induced constriction of the intracortical blood vessels of the brain slices was observed with differential interference contrast microscope. Measurements of the luminal diameter were made on-line during the course of the experiment and confirmed off-line from the stored images. In order to observe whether histamine H1 and H2 receptors affected histamine-induced constriction, the intracortical blood vessels in the brain slices were pre-treated with H1 receptor antagonist diphenhydramine and H2 receptor antagonist cimetidine.

RESULTSExpression of H1 and H2 receptors was detected in the intracortical blood vessels of the rat brain. Histamine (1-100 micromol/L) induced a concentration-dependent constriction from (1.48-/+0.67)% to (32.91-/+7.91)%. The reactions to each histamine concentration were significantly (P<0.01) different from each other, with the exception of the highest histamine concentrations (30 and 100 micromol/L) when maximal constriction due to histamine were observed (P>0.05). With pre-treatment of the slice with 10 micromol/L diphenhydramine, application of histamine did not elicit constriction. Pre-treatment of the slice with 10 micromol/L cimetidine did not completely inhibit but somehow significantly weakened vascular constriction in response to histamine treatment at 10 and 30 micromol/L (P<0.05).

CONCLUSIONHistamine can induce constriction of the intracortical blood vessels, which is mediated by H1 receptor.

Animals ; Blood Vessels ; drug effects ; metabolism ; physiology ; Cerebral Cortex ; blood supply ; Cimetidine ; pharmacology ; Diphenhydramine ; pharmacology ; Histamine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; In Vitro Techniques ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; metabolism ; physiology ; Receptors, Histamine H2 ; metabolism ; physiology ; Vasoconstriction ; drug effects

AIMTo determine the effect of histamine on ischemia-induced cellular edema and viability reduction in rat hippocampal slices, and the involved subtypes of histamine receptor in this effect.

METHODSIn vitro ischemic injury of hippocampal slices was induced by oxygen-glucose deprivation (OGD). The slice injury was determined by real-timely measuring the changes of light transmittance (LT) for the cellular edema in CA1 region of the hippocampal slice, and by detecting the product of 2, 3, 5-triphenyltetrazolium chloride (TTC), formazan, for the slice viability. The effect of histamine at various concentrations on the slice injury was observed, and the blockage by antagonists of histamine receptors was also investigated.

RESULTSHistamine (0.01-10 micromol x L(-1)) inhibited the peak value of LT during OGD in hippocampal slices and improved the reduced viability after OGD. Diphenhydramine (0.1-10 micromol x L(-1)), an H1 receptor antagonist, did not affect the effect of histamine, while cimetidine (0.1-10 micromol x L(-1)), an H2 receptor antagonist, partly abolished the protective effect of histamine.

CONCLUSIONHistamine protects hippocampal slices against ischemia-induced cellular edema and viability reduction; this effect might be mediated via, at least partly, H2 receptor.

Animals ; Cell Hypoxia ; Cell Survival ; drug effects ; Cimetidine ; pharmacology ; Diphenhydramine ; pharmacology ; Formazans ; metabolism ; Glucose ; deficiency ; Hippocampus ; drug effects ; metabolism ; pathology ; Histamine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Male ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley