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Reproductive and Developmental Medicine 2023年第2期7卷 65-67页

作者： Jia-Lei Zhu Jing Jin Jing Tang Department of Pharmacy Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China

Patients infected with coronavirus disease 2019(COVID-19)have high serum levels of proinflammatory cytokines.The"cytokine storm"has become one of the major causes of death for critically ill patients infected by COVID-19.Glucocorticoids,plasma from convalescent patients,blood purification,and tocilizumab are currently recommended for use when the body’s inflammatory response is overactivated.However,there are limitations in terms of medicinal effects,equipment reserves,and treatment expense.These challenges prompted us to assess classical agents with good safety and mature production technology.A recent study showed that nucleotide-binding oligomerization domain(NOD)-,leucine-rich repeat(LRR)-,and pyrin domain-containing protein 3(NLRP3)inflammasomes drive COVID-19 pathology.We speculate that suppression of NLRP3 inflammasome-derived cytokine production may be beneficial in COVID-19-infected patients.dopamine receptors are present in almost all immune cells and can modulate their activation,proliferation,and cytokine production of immune cells.Previous studies have shown that dopamine receptor agonists can control systemic inflammation through inhibition of the NLRP3 inflammasome.This suggests that dopamine receptor agonists may be a new strategy for the treatment of overactive immune responses in COVID-19 patients.This is worthy of further investigation in clinical practice.

关键词： NLRP3 inflammasome Cytokine storm COVID-19 dopamine receptors Medication regimen Interleukin

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dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice

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Current Zoology 2023年第6期69卷 682-693页

作者： Lai-Fu Li Zi-Lin Li Bai-Lin Song Yi Jiang Yan Wang Hua-Wei Zou Lun-Guang Yao Ying-Juan Liu Henan Key Laboratory of Insect Biology in Funiu Mountain Henan International Joint Laboratory of Insect BiologyCollege of Life Science and Agricultural EngineeringNanyang Normal UniversityNanyang 473061HenanChina Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology College of Life Science and AgricultureNanyang Normal UniversityNanyang 473061HenanChina

Social hierarchy greatly influences behavior and health.Both human and animal studies have signaled the medial prefrontal cortex(mPFC)as specifically related to social hierarchy.dopamine D1 receptors(D1Rs)and D2 receptors(D2Rs)are abundantly expressed in the mPFC,modulat-ing its functions.However,it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy.Here,using a confrontation tube test,we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation.Lower rank individuals showed social anxiety together with decreased serum testosterone levels.D2R expression was significantly downregulated in the dorsal part of mPFC(dmPFC)in lower rank individuals,whereas D1R expression showed no significant difference among the rank groups in the whole mPFC.Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test.Finally,simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant-subordinate relationship.The above results indicate that D2Rs in the dmPFC play an important role in social dominance.Our findings provide novel insights into the divergent func-tions of prefrontal D1Rs and D2Rs in social dominance,which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.

关键词： dopamine receptors medial prefrontal cortex social dominance social hierarchy tube test

Identification of human dopamine receptors agonists from Chinese herbs

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Acta Pharmacologica Sinica 2007年第1期28卷 132-139页

作者： Yi-lin ZHANG~(1,2,3,4) Hai-qing ZHANG~(1,2,3,4) Xiao-yu LIU~3 Shi-neng HUA~3 Lu-bing ZHOU~3 Jun YU~2 Xue-hai TAN~(3,5)1 Graduate School of the Chinese Academy of Sciences,Beijing 100039,China 2 Beijing Genomics Institute,Chinese Academy of Sciences Beijing 101300,China 3 HD Biosciences Co Ltd,Shanghai 201203,China Graduate School of the Chinese Academy of Sciences Beijing China Beijing Genomics Institute Chinese Academy of Sciences Beijing China HD Biosciences Co Ltd Shanghai China

Aim:To find human dopamine receptors,especially Dl-like receptor specific ago-nists from Chinese herbs as potential antihypertension drug leads.Methods:TwoD l-like receptor cell lines carrying a μ-lactamase reporter gene,and a D2 receptorcell line coexpressing a promiscuous G protein G15 were constructed using HEK293cells.A natural compound library made from fractionated samples of herbal ex-tracts was used for high-throughput screening（HTS）against one of the cell lines,HEK/D5R/CRE-blax.The interested hits were evaluated for their activities againstvarious dopamine receptors.Results:Fourteen hits were identified from primaryscreening,of which 2 of the better hit samples,HD0522 and HD0059,were selectedfor further material and activity analysis,and to obtain 2 compounds that ap-peared as 2 single peaks in HPLC,HD0522H01 and HD0059H01.HD0059H01could activate D 1,D2,and D5 receptors,with EC50values of 2.28 μg/mL,0.85 μg/mL,and 1.41 μg/mL,respectively.HD0522H01 could only activate DlR and D5Rwith EC50values of 2.95 μg/mL and 8.38 μg/mL.Conclusion:We established cell-based assays for 3 different human dopamine receptors and identified specificagonists HD0522H01 and HD0059H01 through HTS.The specific agonist to D1-like receptors,HD0522H01,may become a new natural product-based drug leadfor antihypertension treatment.

关键词： dopamine receptors natural products high throughput screening hypertension

dopamine: an immune transmitter

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Neural Regeneration Research 2020年第12期15卷 2173-2185页

作者： Sarah Thomas Broome Krystal Louangaphay Kevin AKeay Gian Marco Leggio Giuseppe Musumeci Alessandro Castorina Laboratory of Cellular and Molecular Neuroscience(LCMN) School of Life ScienceFaculty of ScienceUniversity of Technology SydneySydneyAustralia Laboratory of Neural Structure and Function(LNSF) School of Medical Sciences(Anatomy and Histology)Faculty of Medicine and HealthUniversity of SydneySydneyAustralia Section of Pharmacology Department of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly Section of Human Anatomy and Histology Department of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly

The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.

关键词： astrocyte autoimmune disease dopamine dopamine receptors D3R immune transmitter microglia multiple sclerosis neuroinflammation Parkinson’s disease

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Cocaine-induced structural remodeling of dendrites and spines are coordinately regulated by dopamine receptors and NMDA receptors

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Cocaine-induced structural remodeling of dendrites and spine...

中国病理生理学会受体和信号转导专业委员会暨消化专业委员...

作者： Lei Zhang Bin Wang Lin Zhang Zhitao Zhou Yong Jiang Lu Zhang Key Laboratory of Proteomics of Guangdong Province,Department of Pathophysiology,Southern Medical University,Guangzhou 510515,China

＜正＞Drug addiction is a long-lasting condition involving persistent neuroadaptations in the brain. Repeated exposure to cocaine can induce long-term changes in brain.The nature of persistent cocaine-induced neuroadaptations is of interest because they are thought to be involved in the development of dependence and addiction.The brain dopamine （DA） system that originates from the midbrain and projects to the nucleus accumbens （NAc）,caudoputamen （CPu）,and other forebrain structures is a key neural substrate for mediating persistent changes induced by repeated exposure to abused drugs.Besides dopamine,glutamate projections from the prefrontal cortex to the striatum is also required for the behavioral sensitization induced by psychostimulants.Meanwhile,the mitogen-activated protein kinase pathway （MAPK） has been implicated in mediating the rewarding effects of abused drugs.There have been reported that repeated treatment with cocaine increases dendrites branching and the density of dendritic spines in nucleus accumbens （NAc）,caudoputamen （CPu）.However,the molecular mechanisms underlying these structural changes are largely unknown.In this study,we show that both dopamine receptors and NMDA receptors are involved in cocaine-induced structural remodeling of dendrites and spines in CPu and NAc.Moreover,the activation of NMDA receptors is oppositely regulated by DI and D3 dopamine receptors after cocaine treatment.Furthermore,the regulation of dopamine receptors and NMDA receptors on cocaine-induced structural remodeling depends on ERK.These results suggest that cocaine-induced structural remodeling of dendrites and spines are coordinately regulated by dopamine receptors and NMDA receptors.＜正＞Drug addiction is a long-lasting condition involving persistent neuroadaptations in the brain. Repeated exposure to cocaine can induce long-term changes in brain.The nature of persistent cocaine-induced neuroadaptations is of interest because they are thought to be involved in the development of dependence and addiction.The brain dop

关键词： dendrites dendritic spines neuroplasticity dopamine receptors NMDA receptors

Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients

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Acta Pharmacologica Sinica 2006年第8期27卷 966-970页

作者： Sheng-nan WU~(2,3,5,6) Rui GAO~(2,3,6) Qing-he XING~(2,3,6) Hua-fang LI~4 Yi-feng SHEN~4 Niu-fan GU~4 Guo-yin FENG~4 Lin HE~(2,3,7)2 Bio-X Life Science Research Center,Shanghai Jiaotong University,Shanghai 200030,China 3 Institute of Nutritional Sciences,SIBS,Chinese Academy of Sciences,Shanghai 200031,China 4 Shanghai Institute of Mental Health,Shanghai 200030,China 5 Shanghai Institute of Hypertension,Ruijin Hospital,Medical School of Shanghai Jiaotong University,Shanghai 200025,China Bio-X Life Science Research Center Shanghai Jiaotong University Shanghai China Institute of Nutritional Sciences SIBS Chinese Academy of Sciences Shanghai China Shanghai Institute of Hypertension Ruijin Hospital Medical School of Shanghai Jiaotong University Shanghai China Shanghai Institute of Mental Health Shanghai China

Aim:Extrapyramidal syndrome (EPS) is most commonly affected by typical antip-sychotic drugs that have a high affinity with the D2 receptor.Recently,manyresearch groups have reported on the positive relationship between the geneticvariations in the DRD2 gene and the therapeutic response in schizophrenia pa-tients as a result of the role of variations in the receptor in modulating receptorexpression.In this study,we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients.Methods:We identified seven SNP(singlenucleotide polymorphism) (-141Cins>del,TaqIB,TaqID,Ser311Cys,rs6275,rs6277and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87without EPS according to the Simpson-Angus Scale) treated with chlorpromazineafter 8 weeks.The alleles of all loci were determined by PCR (polymerase chainreaction).Results:Polymorphisms TaqlD,Ser311Cys and rs6277 were not poly-morphic in the population recruited in the present study.No statistical signifi-cance was found in the allele distribution of-141Cins>del,TaqIB,rs6275 andTaqIA or in the estimated haplotypes (constituted by TaqIB,rs6275 and TaqIA) inlinkage disequilibrium between the two groups.Conclusion:Our results did notlend strong support to the view that the genetic variation of the DRD2 gene playsa major role in the individually variable adverse effect induced by chlorpromazine,at least in Chinese patients with schizophrenia.Our results confirmed a previousstudy on the relationship between DRD2 and EPS in Caucasians.

关键词： dopamine receptors basal ganglia disease polymorphism chlorpromazine schizophrenia

Histamine postsynaptically excites dopamine D1 and D2 receptor-expressing striatal neurons via H1 and H2 receptors in rats

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Histamine postsynaptically excites dopamine D1 and D2 recept...

中国神经科学学会第十二届全国学术会议

作者： Qian-Xing ZHUANG Han-Ting XU Xu-Juan LU Bin LI Wing-Ho YUNG Jian-Jun WANG Jing-Ning ZHU State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology School of Life Sciences Nanjing University Nanjing Institute of Visual Arts School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong

The central histaminergic nervous system, originating from the tuberomammillary nucleus（TMN） of the hypothalamus, widely innervates almost the whole brain, including the basal ganglia. Here, by using anterograde tracing, immunostaining and patch clamp recording techniques, we investigate the histaminergic afferents in the striatum, the major input structure of the basal ganglia, as well as the effect of histamine on the striatal GABAergic medium spiny projection neurons（MSNs）. We report a direct histaminergic projection from the hypothalamic TMN to the striatum. Furthermore, histamine exerts a postsynaptic excitatory effect on both dopamine D1 and D2 receptor-expressing MSNs. The concentration-response curves and the EC50 values for histamine on two types of MSNs are similar. In addition, both histamine H1 and H2 receptors are co-localized on dopamine D1 and D2 receptor-expressing MSNs, and comediate the histamine-induced excitation on two types of neurons. These results suggest that the histaminergic afferent inputs in the striatum may modulate both dopamine D1 and D2 receptor-expressing MSNs by activation of postsynaptic histamine H1 and H2 receptors and thus function as an important extrastriatal modulator for the direct and indirect pathway of the basal ganglia.

关键词： Histamine Striatum Medium spiny neurons Histamine receptors dopamine receptors

Effects of D2 receptor antagonist haloperidol on hippocampal neuronal apoptosis in a rat model of temporal epilepsy

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Neural Regeneration Research 2008年第10期3卷 1060-1064页

作者： Songqing Wang Aihua Zhang Haitang Chen Qianghua He Peizeng Xie Yiquan Ke Xiaodan Jiang Department of Neurosurgery the 422 Hospital of Chinese PLA Zhanjiang 524005 Guangdong Province China Department of Neurosurgery Zhujiang Hospital Southem Medical University Guangzhou 510282 Guangdong Province China

BACKGROUND： dopamine receptors are divided into D1 and D2 subgroups. It has been reported that D2 receptors resist neural toxicity induced by excitatory amino acids and muscarine, and also alleviate epilepsy attacks following pilocarpine treatment. However, it has not yet been established whether D2 receptors regulate temporal epilepsy. OBJECTIVE： To observe the effects of the D2 antagonist haloperidol on hippocampal neuronal apoptosis and electrical brain activity in a rat model of kainic acid-induced temporal epilepsy. DESIGN, TIME AND SETTING： Randomized grouping and histopathological study were performed at the Neurology Medicine Institute of Zhujiang Hospital, Southern Medical University from August to December 2004. MATERIALS： Twenty-five adult, male, Sprague Dawley rats were selected for the present study. Kainic acid （Sigma, USA） was injected into the right lateral ventricle to establish models of temporal epilepsy. A PowerLah multiplying channel eleetrophysiolograph was provided by AD Instruments, Australia. METHODS： The rats were randomly divided into 5 groups （n = 5）： control, model, haloperidol hippocampus, haloperidol striatum, and haloperidol substantia nigra. Temporal epilepsy was established in all rats except the control group. Haloperidol was slowly injected into the hippocampus, striatum and substantia nigra, respectively, in three different injection groups. Normal saline was injected into the right lateral ventricle of the control rats. MAIN OUTCOME MEASURES： Hippocampal apoptosis was observed on the day 3 of treatment using TUNEL staining. Changes in electroencephalogram at 0, 0.5, 2, 6, and 12 hours following treatment onset were observed using a PowerLab multiplying channel electrophysiolograph. Animal behaviors were classified according to the Racine criteria. RESULTS： Twenty-five rats were included in the final analysis. Seizures did not occur in the control group. In the model group, 10 minutes after kainic acid injection to the lateral cerebral ventricle, epilepsy seizures occurred and

关键词： dopamine receptors kainic acid temporal epilepsy

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Regulation of Gastric-derived dopamine on Duodenal Epithelial Ion Transport in Rats

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Regulation of Gastric-derived Dopamine on Duodenal Epithelia...

中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：冯小燕朱进霞首都医科大学基础医学院生理与病理生理学系消化生理实验室

Background and Aims:Gastric epithelial cells are able to synthesize dopamine(DA),which plays an important role in the gastrointestinal mucosa protection.However,the mechanism is largely unknown.The present study aims to investigate the mechanism underlying the effect of gastric-derived DA and DA receptors on the duodenal epithelial ion transport in rats.Methods:In vivo gastric perfusion,radioimmunoassay,ultra pressure liquid chromatography-mass spectrometry,immunofluorescence,short-circuit current(ISC),real-time p H titration,p H-sensitive fluorescent probes(BCECF-AM)and human D5 receptor transgenic mice were used in the present studies.Results:Immunofluorescence showed that the DAT-immunoreactivity(IR)was remarkably distributed in the H+-K+-ATPase-IR mucosal cells in rat gastric corpus,suggesting the parietal cells are dopaminergic.Intravenous infusion of histamine(2mg/kg/h,n=9,preceptors(D15)were distributed in the duodenal epithelia with clear D5-IR(i.e.D1b)at both apical and basolatoral membranes,and D2-IR(including D2,D3,D4)at the apical membrane in Brunner’s glands and duode

关键词： dopamine dopamine receptors duodenal mucosa secretion real-time p H titration short-circuit current（ISC）

Exploring how primary cilia regulate neuronal activity and brain function

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Exploring how primary cilia regulate neuronal activity and b...

中国神经科学学会第十二届全国学术会议

作者： Nan Wu Xiao-Bing Yuan Wei Gao Shuang-Yi Xie Jing-Yan Jia Key Laboratory of Brain Functional Genomics Ministry of Education/Shanghai Key Laboratory of Brain Functional Genomics East China Normal University

Objective: Most neurons in the brain have a single primary cilium, which is a tiny cell surface protrusion with the accumulation of a group of important receptors, ion channels, and signaling molecules. Primary cilia neural stem cell/progenitor cells are known to regulate neuronal genesis by mediating sonic hedgehog signaling during brain development. However, till now the role of cilia in postmitotic neurons remains a mystery. The present study aims to explore whether primary cilium can affect neuronal activity and animal behavior, and clarify the underlying molecular mechanisms. Methods: We took advantage of mouse genetics technology to specifically ablate the cilium of forebrain pyramidal neurons and parvalbumin-positive interneurons, respectively, and clarify its effect on the morphology and electrophysiological properties of neurons, and its impact on animal behavior. Digital Gene Expression Tag Profiling, RT-PCR and Western blotting were further carried out to dissect the signaling mechanism associated with cilium’s function in neurons. Results:（1） Cilia of postmitotic pyramidal neurons in the forebrain were specifically ablated using the Cre-loxp system（Nex-Cre::IFT88 f/f）.（2） The basic locomotion level of KO mice was significantly reduced.（3） The KO mice showed a lower anxiety level compared with wild type littermates.（4） The transcriptional level of DRD1 and DRD2 were both increased in prefrontal cortex.Conclusion: Our preliminary results suggest that primary cilium on pyramidal neurons may modulate neuronal activity and animal behavior by regulating the function of dopamine receptors.

关键词： dopamine receptors G protein-coupled receptors primary cilium animal model