Expressions of histamine receptors in pediatric mid-urethral striated muscles and mouse striated myogenesis / 中华实用儿科临床杂志

Objective To explore the expressions of histamine receptor subtypes (H1, H2, H3, H4 receptor) in children's mid-urethral striated muscles and during mouse C2C12 striated myogenesis.Methods Children's mid-urethral striated muscle samples were paraffin embedded and tissue sections were made, then immunohistochemical staining was used to check H1, H2, H3, H4 receptors.C2C12 myogenesis was induced, the early differentiation early markers of desmin, middle marker of myogenin, late marker of myosin heavy chain and histamine 4 receptor subtype mRNA were checked by quantitative real-time polymerase chain reaction.Immunofluorescence staining was done to check 3 differentiation markers and histamine H3 receptor protein.Results During myogenesis, the expression of desmin mRNA in the differentiation of 2,4,6 days were 12,68,60 times as many as that of the undifferentiated myoblasts;the expression of myogenin mRNA in the differentiation of 2,4,6 days were 631,1 408,914 times as many as that of the undifferentiated myoblasts;the expression of myosin heavy chain mRNA in the differentiation of 2,4,6 days were 7 718,9 448,286 288 times as many as that of the undifferentiated myoblasts.The expression level of H1 receptor mRNA in the differentiation of 6 days was about 25％ to undifferentiated cells;the expression of H2 receptor mRNA in undifferentiated cells and differentiated cells groups had no significant difference (F =1.47, P ＞ 0.05);the expression of H3 receptor mRNA in the differentiation of 2,4,6 days was 28,103,198 times to undifferentiated cells;H4 receptor mRNA was not detected.In immunofluorescence staining, H3 receptor protein staining intensity increased with the differentiation.Immunohistochemistry of pediatric urethral striated staining indicated that H1, H2, H3 receptor staining was positive,H1 receptor showed strong positive staining, H3 receptor moderate positive staining,and H2 receptor showed weak positive staining.Conclusions Histamine receptor subtypes of H1 receptor, H2 receptor and H3 receptor were found during mouse striated myogenesis and in the children's mid-urethral striated muscles.The increasing expression of H3R with myogenesis might indicate it plays a role in mature striated muscle cells.

Histamine H3 receptor inhibited electrically evoked cytoplasmic calcium in differentiated skeletal C2C12 myoblasts / 中国病理生理杂志

AIM:To explore the expression and possible function of histamine H3 receptor (H3R) in striated myogenesis and the differentiated C2C12 cells.METHODS: H3R and myogenesis late marker myosin heavy chain (MHC) were detected at mRNA and protein levels during C2C12 myogenesis.H3R antagonist ciproxifan was added and the expression of the myogenesis early marker desmin, intermediate markers myogenin and MHC was detected.Differentia-ted myoblasts were loaded with Fluo-4 calcium indicator dye and the effect of R-( a)-methylhistamine ( RMeHA) on the cy-toplasmic calcium concentration was determined under the 200 mA electrical stimulation.RESULTS: The expression of H3R and MHC was increased during myogenesis.Ciproxifan incubation had no influence on the 3 striated myogenesis mar-kers (P>0.05).In C2C12 myoblasts, RMeHA (10 nmol/L~100 μmol/L) effectively diminished cytoplasmic calcium peak when the cells were electrically paced (P<0.05).The best inhibitory effect of RMeHA was observed at dose of 100 nM for 10 min and 20 min, which was higher than that for 5 min (P<0.05).CONCLUSION: H3R might have little effect on the myogenic differentiation, but diminishes cytoplasmic calcium peak of the differentiated myoblasts under electri-cal stimulation.

Neuromodulación e histamina: regulación de la liberación de neurotransmisores por receptores H3 / Neuromodulation and histamine: regulation by H3 receptors of neurotransmitter release

Histamine regulates at the pre- and post-synaptic levels several functions of the mammalian Nervous System, in which three (H1, H2, and H3) out of the four G protein-coupled histamine receptors cloned so far are widely distributed. The histamine H3 receptor (H3R) was first identified as an auto-receptor controlling histamine synthesis and release, but several lines of evidence have shown the H3R to regulate as a hetero-receptor the release of a number of neuroactive substances, namely acetylcholine, 5-hydroxytryptamine (5-HT, serotonin), noradrenaline, dopamine, glutamate, y-aminobutyric acid (GABA) and the neuropeptides sustance P and calcitonin gene-related peptide (CGRP). H3R-mediated regulation of the release of these neurotransmitters and neuro-modulators, both in normal and pathological conditions, suggest that drugs acting at the receptor may have therapeutic use in a number of diseases such as sleep disorders, ischemia-induced cardiac arrhythmias, migraine, obesity, Alzheimer's disease and schizophrenia.

La histamina regula a nivel pre y postsináptico diversas funciones del Sistema Nervioso de los mamíferos, el cual expresa de manera abundante tres (H1, H2 y H3) de los cuatro receptores a histamina acoplados a proteínas G descritos a la fecha (H1-H4). El receptor a histamina H3 (H3R) se identificó inicialmente como el autorreceptor responsable del control de la liberación y la síntesis de la histamina. Posteriormente se estableció que este receptor se encuentra también en las terminales axónicas de otras neuronas del Sistema Nervioso Central y periférico, donde regula como heterorreceptor la liberación de varios transmisores. En este trabajo se revisan los efectos de la activación del H3R en la liberación de histamina, acetilcolina, 5-hidroxitriptamina (5-HT, serotonina), noradrenalina, dopamina, glutamato, ácido y-aminobutírico (GABA) y los neuropéptidos sustancia P y el péptido relacionado al gen de la calcitonina (CGRP). La regulación por el receptor H3 de la liberación de estos neurotransmisores y neuromoduladores, tanto en condiciones normales como patológicas, sugiere que los fármacos que actúen sobre dicho receptor pueden tener uso terapéutico en alteraciones diversas como los transtornos del sueño, las arritmias cardiacas causadas por isquemia, la migraña, la obesidad, la enfermedad de Alzheimer y la esquizofrenia.

L-histidine enhances learning in stressed zebrafish

The aim of the present study was to determine the effect of the histaminergic precursor L-histidine and the H3 receptor antagonist thioperamide on the learning process of zebrafish submitted or not to confinement stress. On each of the 5 consecutive days of experiment (D1, D2, D3, D4, D5), animals had to associate an interruption of the aquarium air supply with food offering. Non-stressed zebrafish received an intraperitoneal injection of 100 mg/kg L-histidine, 10 mg/kg thioperamide or saline after training. Stressed animals received drug treatment and then were submitted to confinement stress for 1 h before the learning procedure. Time to approach the feeder was measured (in seconds) and was considered to be indicative of learning. A decrease in time to approach the feeder was observed in the saline-treated group (D1 = 141.92 ± 13.57; D3 = 55 ± 13.54), indicating learning. A delay in learning of stressed animals treated with saline was observed (D1 = 217.5 ± 25.66). L-histidine facilitated learning in stressed (D1 = 118.68 ± 13.9; D2 = 45.88 ± 8.2) and non-stressed (D1 = 151.11 ± 19.20; D5 = 62 ± 14.68) animals. Thioperamide inhibited learning in non-stressed (D1 = 110.38 ± 9.49; D4 = 58.79 ± 16.83) and stressed animals (D1 = 167.3 ± 26.39; D5 = 172.15 ± 27.35). L-histidine prevented the increase in blood glucose after one session of confinement (L-histidine = 65.88 ± 4.50; control = 53 ± 3.50 mg/dL). These results suggest that the histaminergic system enhances learning and modulates stress responses in zebrafish.

Anti-convulsion action of histamine H3 receptor antagonists to rat model with intractable epilepsy / 吉林大学学报(医学版)

Objective To explore the anti-convulsion action of histamine(HA) in the central system and treatment of histamine H3 receptor(H3R) antagonists to rat model with intractable epilepsy.Methods 88 Wistar rats(12-day-old) were randomly divided into three groups:normal control group,N-methyl-D-aspartate(NMDA) group and betahistine(BH) groups(including high and low dose BH groups).Wistar rats received an intraperitoneal NMDA administration to make animal model of intractable epilepsy at infant period and toddler age.After that,the rats were observed daily for latencies and incidences to two NMDA-dependent stereotypical behaviors.The HA content of each brain region was determined with fluorimetry,and H3R were evaluated with immunohistochemical method.Results The automatisms including tail twisting and emprosthotonus seizures of(12-17)-day-old rats were observed in NMDA and BH groups.The rats,aged 18-25 d,became quiet following automatisms rather than emprothotonic.Compared with NMDA group,BH groups had longer latencies and lower incidences of tail twisting and emprosthotonus(P0.05).Conclusion The NMDA-induced model is similar to the clinical manifest of human West syndrome.It is up to animal model of intractable epilepsy at infant period and toddler age.The HA content of brain region is negatively related with seizure incidence.H3R antagonists have certain therapeutic function to intractable epilepsy in rats at infant period and toddler age.

Modulatory effect of histamine H_3 receptor on cardiovascular system / 中国药理学通报

The intracellular signal transduction pathway of histamine H 3 receptor was reviewed. The modulatory effect to some neurotransmitters on cardiovascular system and the therapeutic potential of histamine H 3 receptor agonist was summarized.

An Observation of Antihistamine & Anti- inflammation Drugs on Pathological Changes of Early Pulmonary Edema in Experimental Respiratory Burns / 第三军医大学学报

This article is to report our observation of the therapeutic effect of antihista-mine and anti-inflammation drugs on the early pulmonary edema in respiratory burns. Thirty-two dogs were employed in the experiment and divided into 4 groups: Group Ⅰconsisted of 8 dogs which were inflicted with respiratory tract burns without any treatment and served as the control.Group Ⅱ: 8 animals received H1H2 receptor antagonists of benadryl and cime-tidine after the burns.Group Ⅲ: 8 animals were treated with indomethacin after the burns.Group Ⅳ: 8 animals were treated with dexamethasome after the burns.It was found that under conventional light microscope the interstitial pulmonary edema in GroupⅡ was the mildest and the alveolar edema in both Groups Ⅱ and Ⅲ was milder than in the other two. The difference between Groups Ⅰ and Ⅱ was statistically significant(P