权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Physiology and Pharmacology of BRS3 (Bombesin Receptor Subtype-3)

BRS3（铃蟾肽受体亚型 3）的生理学和药理学

基本信息

批准号：
10919485
负责人：
MARC L REITMAN
金额：
$ 38.47万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10919485
关键词：
Ablation Acute Affinity Agonist Alpha Cell Area Beta Cell Biology Blood Pressure Body Temperature Body Weight Bombesin Bombesin Receptor Brain Brain Stem Cannabinoids Cardiovascular Diseases Cell Line Cell Nucleus Cholelithiasis Cre driver Degenerative polyarthritis Drug Kinetics Dyslipidemias Eating Effectiveness Fasting Feedback G-Protein-Coupled Receptors Genetic Genetic Transcription Glucose Goals Health Heart Rate Homeostasis Hypertension Hypothalamic structure Islets of Langerhans Knock-out Leptin Life Expectancy Ligands Malignant Neoplasms Midbrain structure Mus Names Neurons Non-Insulin-Dependent Diabetes Mellitus Obesity Oral Pathway interactions Pharmacology Physiology Population Preoptic Areas Regulation Research Rest Risk Rodent Role Signal Pathway Sympathetic Nervous System attenuation bombesin receptor subtype 3 combinatorial comorbidity complement pathway improved insulin secretion interest member metabolic rate mouse genetics neuropeptide Y obesity treatment paraventricular nucleus recombinase reduced food intake

项目摘要

Progress in FY2023 includes the following: We have identified preoptic area neurons expressing BRS3 (POA-BRS3) as a population whose activation increased body temperature; inversely, acute inhibition of these neurons reduced body temperature. POA-BRS3 neurons that project to either the paraventricular nucleus of the hypothalamus or the dorsomedial hypothalamus increased body temperature, heart rate, and blood pressure via the sympathetic nervous system. Long-term inactivation of POA-BRS3 neurons caused increased body temperature variability, overshooting both increases and decreases in body temperature set point, with RNA expression profiles suggesting multiple types of POA-BRS3 neurons. Thus, POA-BRS3 neuronal populations regulate body temperature and heart rate, contribute to cold defense, and fine-tune feedback control of body temperature. These findings advance understanding of homeothermy, a defining feature of mammalian biology. We are now generating Brs3-FlpO and Brs3-Dre recombinase driver mouse lines. These enable combinatorial approaches to identifying and determining the functions of smaller populations of neurons that are better defined.

二零二三财年的进展包括以下各项：我们已经确定视前区神经元表达BRS 3（POA-BRS 3）作为一个人口的激活增加体温，相反，急性抑制这些神经元降低体温。投射到下丘脑室旁核或背内侧下丘脑的POA-BRS 3神经元通过交感神经系统增加体温、心率和血压。POA-BRS 3神经元的长期失活导致体温变异性增加，超过体温设定点的增加和降低，RNA表达谱表明多种类型的POA-BRS 3神经元。因此，POA-BRS 3神经元群体调节体温和心率，有助于寒冷防御，并微调体温的反馈控制。这些发现促进了对恒温的理解，恒温是哺乳动物生物学的一个定义性特征。我们现在正在产生Brs 3-FlpO和Brs 3-Dre重组酶驱动小鼠系。这些使组合方法能够识别和确定更好定义的较小神经元群体的功能。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways.

DOI：
10.1016/j.cmet.2021.05.001
发表时间：
2021-07-06
期刊：
Cell metabolism
影响因子：
29
作者：
Piñol RA;Mogul AS;Hadley CK;Saha A;Li C;Škop V;Province HS;Xiao C;Gavrilova O;Krashes MJ;Reitman ML
通讯作者：
Reitman ML

The effects of housing density on mouse thermal physiology depend on sex and ambient temperature.

DOI：
10.1016/j.molmet.2021.101332
发表时间：
2021-11
期刊：
Molecular metabolism
影响因子：
8.1
作者：
Škop V;Xiao C;Liu N;Gavrilova O;Reitman ML
通讯作者：
Reitman ML

Preoptic bombesin-like receptor-3 neurons heat it up.

视前铃蟾肽样受体 3 神经元将其加热。

DOI：
10.1080/23328940.2022.2047574
发表时间：
2022
期刊：
Temperature (Austin, Tex.)
影响因子：
0
作者：
Piñol,RamónA;Reitman,MarcL
通讯作者：
Reitman,MarcL

FGF21 mimetic shows therapeutic promise.

DOI：
10.1016/j.cmet.2013.08.014
发表时间：
2013-09-03
期刊：
Cell metabolism
影响因子：
29
作者：
Reitman ML
通讯作者：
Reitman ML

Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists.

吡啶磺酰脲类和吡啶磺酰胺类作为选择性铃蟾肽受体亚型 3 (BRS-3) 激动剂。

DOI：
10.1016/j.bmcl.2011.02.011
发表时间：
2011
期刊：
Bioorganic & medicinal chemistry letters
影响因子：
2.7
作者：
Lo,MichaelM-C;Chobanian,HarryR;Palyha,Oksana;Kan,Yanqing;Kelly,TheresaM;Guan,Xiao-Ming;Reitman,MarcL;Dragovic,Jasminka;Lyons,KathrynA;Nargund,RaviP;Lin,LinusS
通讯作者：
Lin,LinusS