Immunological disturbance effect of exogenous histamine towards key immune cells

Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.

A core-satellite self-assembled SERS aptasensor containing a“biological-silent region”Raman tag for the accurate and ultrasensitive detection of histamine

Herein,a novel interference-free surface-enhanced Raman spectroscopy(SERS)strategy based on magnetic nanoparticles(MNPs)and aptamer-driven assemblies was proposed for the ultrasensitive detection of histamine.A core-satellite SERS aptasensor was constructed by combining aptamer-decorated Fe_(3)O_(4)@Au MNPs(as the recognize probe for histamine)and complementary DNA-modified silver nanoparticles carrying 4-mercaptobenzonitrile(4-MBN)(Ag@4-MBN@Ag-c-DNA)as the SERS signal probe for the indirect detection of histamine.Under an applied magnetic field in the absence of histamine,the assembly gave an intense Raman signal at“Raman biological-silent”region due to 4-MBN.In the presence of histamine,the Ag@4-MBN@Ag-c-DNA SERS-tag was released from the Fe_(3)O_(4)@Au MNPs,thus decreasing the SERS signal.Under optimal conditions,an ultra-low limit of detection of 0.65×10^(-3)ng/mL and a linear range 10^(-2)-10^5 ng/mL on the SERS aptasensor were obtained.The histamine content in four food samples were analyzed using the SERS aptasensor,with the results consistent with those determined by high performance liquid chromatography.The present work highlights the merits of indirect strategies for the ultrasensitive and highly selective SERS detection of small biological molecules in complex matrices.

Efficacy and anti-inflammatory analysis of glucocorticoid,antihistamine and leukotriene receptor antagonist in the treatment of allergic rhinitis

BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.

Prescription practice of antihistamines for acute upper respiratory tract infections in pediatric patients in a local emergency department in Hong Kong

BACKGROUND: Currently there is very limited data in the literature assessing the prevalence of antihistamine prescription, and there is no local prevalence data about the prescription of antihistamine agents among primary practitioner and emergency physicians. The objectives are 1) to report the prevalence of antihistamine prescription for children less than 6 years old with acute upper respiratory infection and 2) to explore the associated factors for the prescription practice.METHODS: This is a cross-sectional study. All consecutive cases of paediatric patients aged 6 or below who presented to the emergency department during a study period of one week from April 1 to July 4, 2009 with diagnosis of acute upper respiratory infection were included. Totally 162 patients were included.RESULTS: Among the 162 cases, 141(87%) patients were prescribed one antihistamine of any group. Sixty(37%) patients were prescribed two or more antihistamines. In multivariate logistic regression model, age was found to be signi? cantly(P<0.001) associated with multiple antihistamine prescription(OR=1.042, 95%CI=1.02 to 1.06). Years of graduation of attending physician for more than 5 years was also a strong predictor of multiple antihistamine prescription(OR=4.654, 95%CI=2.20 to 9.84, P<0.001).CONCLUSION: In the local emergency department, patients' age and the years of graduation from medical school of the attending physician were predictors of multiple antihistamine prescription for acute upper respiratory infections for children aged less than 6.

Peripheral mechanism of inhibitory effect of centrally administrated histamine on gastric acid secretion

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Bile acid increases expression of the histamine-producing enzyme,histidine decarboxylase,in gastric cells

AIM:To investigate the effect of bile acid on the expression of histidine decarboxylase(HDC),which is a major enzyme involved in histamine production,and gene expression of gastric transcription factors upon cooperative activation.METHODS:HDC expression was examined by immunohistochemistry,reverse transcriptase polymerase chain reaction,and promoter assay in human gastric precancerous tissues,normal stomach tissue,and gastric cancer cell lines.The relationship between gastric precancerous state and HDC expression induced by bile acid was determined.The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated.MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor(FXR),small heterodimer partner(SHP),and caudal-type homeodomain transcription factor(CDX)1 expression plasmids.The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay.RESULTS:Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases.Here,we show that bile acid increased the expression of HDC,which is a rate-limiting enzyme of the histamine production pathway.FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression.In addition,the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression.We confirmed similar expression patterns for HDC,CDX1,and SHP in patient tissues.CONCLUSION:HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR,SHP,and CDX1.

H_1 and H_2 receptors in the locus ceruleus are involved in the intracere-broventricular histamine-induced carotid sinus baroreceptor reflex reset-ting in rats

Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.

Histamine 3 receptor activation mediates inhibition of acid secretion during Helicobacter-induced gastritis

AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide(THIO)for 12 wk.After treatment,mice were analyzed for morphological changes and gastric acid content.Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction(RTPCR).Location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H + ,K + -ATPase βsubunit. RESULTS:Inflammation and parietal cell atrophy was observed after 12 wk of H.felis infection.Interestingly, treatment with the H3R antagonist thioperamide(THIO) prior to and during infection prevented H.felis-induced inflammation and atrophy.Compared to the uninfected controls,infected mice also had significantly decreased gastric acid.After eradication of H.felis with THIO treatment,gastric acidity was restored.Compared to the control mice,somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection.Despite elevated gastric acid levels, after eradication of H.felis with THIO,somatostatin mRNA was elevated whereas gastrin mRNA was suppressed.Immunofluorescence revealed the presence of H3 receptors on the parietal cells,somatostatin-secreting D-cells as well as the inflammatory cells. CONCLUSION:This study shows that during H.felis infection,gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation.The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin.

Effects of histamine HlR-H4R-agonist on the airway epithelium of rabbits

Objective:To explore the exact role of histamine receptors in respiratory system.Methods: The cohort comprised of six groups(group I control and groupⅡ—Ⅳtreated) containing five rabbits in each group.Control-group received vehicle(sterile distilled water) and treated groups received subcutaneous histamine(100μg/kg,b.i.d.),and H1R-agonist(HTMT),H2R-agonist (amthamine),H3R-agonist(R-(-)-α-methylhistamine) and H4R-agonist(clobenpropit) each in a dose of 10μg/kg,b.i.d.for 30 subsequent days.After completion of treatment,animals were euthanized and perfused with 10% buffered formalin.Small tissue blocks of trachea and lungs were processed for paraffin embedding.Observations were recorded in sample photomicrographs taken from 10μm thick.Haematoxylin and eosin stained sections.Results:It was observed that trachea and bronchi from histamine,H1R and H4R groups had only patches of hyperplastic and hypertrophied epithelium and in general,cells in the affected region were taller heaped up. The bronchiolar epithelia from all treated groups showed hypertrophy and hyperplasia throughout with most of the cells having rounded profile and appeared to bud out from the basal cells. Conclusions:It is concluded that histamine receptors on induction via its specific agonist can induce hypertrophy,hyperplasia of respiratory tract epithelia suggesting its role akin to growth stimulating factor and warranting further long-term study.

Stimulation by nizatidine,a histamine H_2-receptor antagonist,of duodenal HCO_3^-secretion in rats:relation to anti-cholinesterase activity

AIM To examine whether nizatidine stimulatesduodenal HCO3- secretion in rats by inhibitingAChE activity.METHODS Under pentobarbital anesthesia,aproximal duodenal loop was perfused withsaline,and the HCO3 secretion was measuredat pH 7.0 using a pH-stat method and by adding10mM HCI.Nizatidine,neostigmine,carbacholor famotidine was administered i.v.as a singleinjection.RESULTS Intravenous administration ofnizatidine（3-30 mg/kg）dose-dependentlyincreased duodenal HCO3- secretion,and theeffect at 10mg/kg was equivalent to thatobtained by carbachol at 0.01 mg/kg.Thisnizatidine action was observed at the same doserange that inhibited acid secretion and enhancedgastric motility,mimicked by i.v.injection ofneostigmine（0.03 mg/kg）,and significantlyattenuated by bilateral vagotomy and prior s.c.administration of atropine but not byindomethacin,a cyclooxygenase inhibitor,orNG-nitro-L-arginine methyl ester,a NO synthaseinhibitor.The HCO3- secretory response toacetylcholine（0.001 mg/kg）was significantlypotentiated by the concurrent administration ofnizatidine（3mg/kg,i.v.）.The IC50of nizatidine for AChE of rat erythrocytes was1.4×10-6M,about 12 times higher than that ofneostigmine.Neither famotidine(】10-3M,30mg/kg,i.v.)nor cisapride(】 10-3M,3mg/kg,i.v.)had any influence on AChEactivity or duodenal HCO3- secretion.Duodenaldamage induced by acid perfusion（100 mM HCIfor 4 h）in the presence of indomethacin wassignificantly prevented by nizatidine andneostigmine,at the doses that increased theHCO3- secretion.CONCLUSION Nizatidine stimulates duodenalHCO3- secretion,in both vagal-dependent andatropine-sensitive manners,and the action isassociated with the anti-AChE activity of thisagent.

Assay of Histamine in Single Mast Cells by Capillary Zone Electrophoresis with Electrochemical Detection

Capillary zone electrophoresis was employed for the analysis of histamine in single rat peritoneal mast cells using an amperometric detector. In this method, individual mast cells and then 0.02 mol/L NaOH as a lysing solution are injected into the front end of the separation capillary. A cell injector was constructed for easy injection of single cells. Histamine in single mast cells has been identified and quantified.

Neural histamine in the tuberomammillary nucleus regulates the onset of neurogenic pulmonary edema in rabbits

Objective： To explore the effect of neural histamine in the tuberomammillary nucleus（TM） on neurogenic pulmonary edema （NPE） onset in rabbits and the function of the rostral ventrolateral medulla（RVLM） in the neural histamine modulation of NPE. Methods： NPE was produced by the intracisternal injections of fibrinogen and thrombin. The contents of histamine in the TM and RVLM in rabbits were measured with high performance liquid chromatography（HPLC）. Rabbits were placed on a stereotaxic frame and microinjection cannulae were inserted into the TM and RVLM using brain atlas coordinates. Animals were pretreated with R- a -methylhistamine（MeHA） in the TM and chlorphenamine Mmaleate/cimetidine in the RVLM prior to establishing the NPE model. Changes in the lung water ratio and mean arterial pressure（MAP） were recorded, and paraffin sections of lung tissue were observed by light microscope. Results：We found that the contents of histamine（HA） in the TM and RVLM increased significantly with the onset of NPE. Pretreatment with MeHA in the TM and chlorphenamine Mmaleate in the RVLM significantly decreased MAP, and the lung water ratio and histological characteristics of the NPE in the rabbit model. Pretreatment with cimetidine in the RVLM had no effect on NPE. Conculsion：The results suggest that neural histamine in the TM is involved in the onset of NPE, and this effect of neural histamine is mediated by H1 receptor in the RVLM

The role of histamine H4 receptors as a potential targets in allergic rhinitis and asthma

Histamine—the main product of mast cells plays critical role in the pathogenetic pathways of both allergic rhinitis and asthma. The novel concept of the unique airway diseases its only supported by the similarities within pathogenetic process. Antagonists of H1 and H2 receptors are quite effective in allergic rhinitis, but not effective enough in asthma. In an era of corticosteroids, leucotriene antagonists and Anti-IgE treatment, there is still a challenge to search for more effective, more acurate and more safe treatment option. Antagonists (inversive agonists) of histamine receptors H4 seems to be one of the promising targets in the allergic rhinitis and asthma treatment. The first H4 antagonist entered to clinics and the results from a proof-of-concept Phase II clinical study is expected to be disclosed soon. This review article summarizes current knowledge on H4R that have been collected in various studies sharing evidences about efficacy of H4R as a reasonable target for diseases with histamine involved pathogenetic pathways.

Dominance of Enterobacteria among Histamine-Producing Bacteria Isolated from Indian Mackerel

Histamine fish poisoning (HFP) is a major illness occurring throughout the world due to the consumption of quality of deteriorated fish containing pre-formed histamine from bacterial activities. In the study reported here, the histamine-producing bacteria were isolated from the muscle, gills and the gut of 19 samples of Indian mackerel (Rastrelliger kanagurta) from Mumbai, India. The isolates from modified Niven’s medium (MNM) were confirmed for their ability to produce histamine by using 4 different pH-indicator media, followed by HPLC analyses. Out of 202 isolates, 63 isolates produced considerable amounts of histamine on at least 3 out of 4 media used in this study. The histamine formers were identified by biochemical tests followed by sequencing of their 16SrDNA gene, which showed that 89% of the isolates belonged to 13 different genera of the family Enterobacteriaceae. The non-enterobacterial histamine-producing bacteria belonged to the genera Staphylococcus, Alkaligenes, Shewanella and Psychrobacter.

Dose-dependent effect of histamine on antibody generation in vivo

Objective:To delineate immunomodulatory role of histamine on antibody generation pr of ile in rabbit in the present dose-dependent histamine study.Methods:The cohort comprised of three groups(Ⅲ,ⅣandⅤ),containing six rabbits each,and received subcutaneous histamine 50μg/kg×bis in die(b.i.d.),100μg/kg×b.i.d.and 200μg/kg X b.i.d.,respectively for 10 days (starting from the 1st day).They were subsequently immunized on the 3rd day with intravenous injection of sheep blood cell(SRBC)(1×10 cells/mL).GroupⅡ(positive control)(n=6) received vehicle(sterile distilled water) and immunized at day 3 similarly while groupⅠ(negative control) (n=6) remained non-immunized and received only vehicle.All experimentations were performed in triplicate.Blood samples were collected on pre-immunization(pre-I)(day 0),as well as on days 7-,14-,21-,28- and 58- post-immunization(post-I).Immunological parameters[total immunoglobulins(Igs),IgM and IgG]were analyzed by enzyme linked immunosorbent assay (ELISA) technique.Results:Histamine could influence a detectable antibody response to SRBC as early as day 7-post-I,which lasted until day 58- post-I.The results were found statistically significant(P【 0.05).Conclusions:Our results provide evidence that histamine has a short-term effect on antibody generation(until its presence in the body),and the antibody generation titer in vivo were affected by the concentration of histamine.

Evaluation of the Effects of Corticosteroids on Histamine Release by ex Vivo Cutaneous Microdialysis

The purpose of the study was to evaluate the effects of corticosteroids on histamine release and to compare their potency with the MacKenzie classification based on their vasoconstrictor effects. Thanks to ex Vivo cutaneous microdialysis, we studied histamine-induced release over a period of time on excised abdominal skin from women. Eight corticosteroids were topically applied with occlusive dressing onto the skin, above probes, before anti-IgE injection. Histamine levels were assessed by an EIA method. In order to compare the different corticosteroids, AUC was calculated allowing an estimation of the amount of released histamine for 60 min of ex vivo cutaneous microdialysis. Diflucortolone 0.1% and micronized betamethasone dipropionate 0.05% are considered as corticosteroids with high potency in MacKenzie classification. Betamethasone dipropionate associated with propylene glycol 0.05%, belongs to a stronger class in Mackenzie classification. Our results showed that the decrease in histamine release was more important with difluocortolone than with both of these corticosteroids. Therefore there was no correlation between the vasoconstrictor potency of topical corticosteroids and their ability to inhibit histamine release.

The extract of Mucuna pruriens possesses histamine activity

Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle was extracted with 0.0015 M NaCl.Muscle strips of guinea pig ileum were prepared and contractile responses were measured using a Kymograph.Two sets of experiment were conducted:（1）.The contraction of the ileum in presence of different concentrations of histamine,2-methylhistamine and the extract of Mucuna pruriens.（2）.The contractile response of the ileum in presence of different concentrations of the extract and antagonists including diphenhydramine,atropine and methysergide.Results:（1） The extract of Mucuna pruriens hair, 2- methylhistamine and histamine produced dose dependent contraction of guinea pig ileum (Extract ED50 = 13.0μg/mL,2-methylhistamine ED50=8.5μg/mL and histamine ED50=10.0μg/ mL).（2） Diphenhydramine,an H,antagonist competitively blocked the contractile response of the Mucuna pruriens extract（3） Coadminstration of the Mucuna pruriens extract either with different doses of antimuscarinic agent atropine or 5-hydroxytryptamine blocking agent methysergide did not alter the extract induced contractile response of the guinea pig ileum.Conclusion:These results demonstrate that the spines of Mucuna pruriens possess histamine activity which may contribute to its itching and painful irritation effects.

In vivo immunomodulatory profile of histamine receptors(H1,H2,H3 and H4):a comparative antagonists study

Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study.

Role of Histamine H1 Receptors in Vestibular Nucleus in Motion Sickness

Objectives To investigate the expression of histamine H1 receptors （H1R） in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness （MS）. Methods A total of 24 healthy Sprague-Dawley rats were divided randomly into four groups （n=6 each） which determined if the animals would receive induction of MS or drug （promethazine） treatment： MS （ - ）/Drug （ - ）; MS（＋）/Drug （ - ）; MS （ - ）/Drug （ ＋ at 0.25 mg）; and MS （ ＋ ）/ Drug（＋）. MS was induced by complex motion stimulation and the conditioned taste aversion was used as a behavioral indicator of MS. The volume of 0.15% sodium saccharin solution （SS） intake within 45 minutes after motion stimulation was measured. H1R in the vestibular nucleus was examined by immunofluorescence staining. The expression of H 1R protein in brainstem tissue at vestibular nucleus level was detected by western blot. Results The mean SS intake volume in the MS （ ＋ ）/Drug （ - ） group （8.8 ml） was significantly less than that of the MS （ - ）/Drug （ - ） group （15.1 ml） （P 〈 0.01）. The mean SS intake volume of the MS （-）/Drug （＋） group （14.8 ml） was similar to that of the MS（-）/Drug（-） group. The mean SS intake volume （9.6 ml） of the MS（＋）/Drug（＋） group was more than that of the MS（＋）/Drug（-）group （P〈0.01）, but less than that of the MS（-）/Drug（-） group or MS（-）/Drug（＋） group （P 〈 0.01）. Immunofluorescence staining showed positive expression of H1R in the vestibular nucleus of brainstem and the expression was enhanced by motion stimulation. Western blot analysis showed that H1R protein expressed in the brainstem tissue at vestibular nucleus level and the expression also increased significantly after motion stimulation. The MS-induced increase of H1R was not affected significantly by promethazine. Conclusions H1Rs exist in the vestibular nucleus in rats and H 1R expression is up-regulated by motion stimulation, but not affected by promethazine. The findings indicate that the histaminergic system is involved in MS. Promethazine, as an H1R blocker, may play its anti-MS role by competing the binding site on H1Rs with histamine rather than inhibiting H1R expression.

Effects of Supplemental Histamine on Gastric Acid Secretion, Digestive Enzyme Activities, Intestinal Microfloral of Early Weaned Piglets

Two experiments were conducted to study the effect of supplemental histamine in the diet of early-weaned piglets. In experiment A, 24 cross bred piglets with an average body weight of 6.10±0. 40 kg, weaned at the age of 28 days, were divided into four groups, fed with basal diet of low dietary copper without (control) or with supplemental histamine at 60, 120, 180μg kg-1 BW. During the two weeks and the third week after weaning, ADG(average daily gain) of piglets were increased by 15.8%(P<0. 05), 9.5%(P< 0.10) by addition of 60μg kg-1 BW histamine, but decreased by addition of 180μg kg-1BW histamine, which also increased the amount of E. coli in colon and the scour incidence. The secretion of gastric acid and pepsin were improved by both dose of supplemental histamine (60, 180μg kg-1BW) and gastric digesta pH were decreased by both. Addition of 60 μg kg-1 BW histamine improved the activities of trypsin, amylase in duodelum digesta. In experiment B, 12 cross bred piglets with an average body weight of 6. 85±0.35 kg, weaned at the age of 28 days, were divided into two groups, fed with basal diet of high dietary copper without (control) or with supplemental 60 μg kg-1 BW histamine. During the two weeks and the third week after weaning, ADG of piglets were increased by 9. 8% (P<0.05), 7. 0% (P<0. 10). The secretion of gastric acid, activities of trypsin and amylase in duodelum digesta, were also improved by addition of 60 μg kg-1BW histamine. The results showed that addition of histamine (60μg kg-1BW) in early weaned piglets could increase the secretion of gastric acid and pepsin, reduce gastric digesta pH and scour incidence, improve activities of trypsin, amylase in duodelum digesta, and the growing performance of early weaned piglets.