GPR139
- Known as:
- GPR139
- Catalog number:
- Y213953
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- GPR139
Related genes to: GPR139
- Gene:
- GPR139 NIH gene
- Name:
- G protein-coupled receptor 139
- Previous symbol:
- -
- Synonyms:
- PGR3
- Chromosome:
- 16p12.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-05-26
- Date modifiied:
- 2016-10-06
Related products to: GPR139
Related articles to: GPR139
- Wakefulness produces sleep-promoting substances and the cerebrospinal fluid contains substances that reflect homeostatic sleep pressure. However, identities of such molecules, and the neural mechanisms for producing and sensing them, remain mysterious. Here we show that cerebrospinal fluid levels of tryptamine (TrpA) track homeostatic sleep pressure in nocturnal mice and diurnal pigs, reflecting physical activity history independently of light-dark cycles. We developed a ratiometric fluorescent sensor for TrpA and showed that TrpA is produced by wake-active monoaminergic nuclei in the diencephalon and brainstem and is secreted in an activity-dependent manner. We showed that released TrpA binds to G-protein-coupled receptor 139 (GPR139) and enhances neuronal excitability in the hypothalamic preoptic area to promote sleep. TrpA-GPR139 signaling was necessary for homeostatic sleep rebound and small-molecule GPR139 agonists promoted sleep duration and quality. Together, our study reveals TrpA as a signal related to sleep homeostasis and GPR139 as a druggable target against its disruption. - Source: PubMed
Publication date: 2026/06/19
Cao HuatengWang KuiZhao JinZha Zhong-HuaZhang QianXiu YijinWu BangshengHuang ShajinZhu Xiao-NaLi XiaotingChen JiananWen HanPan SiwenYang Ke-XinHu JiYu Jin-TaiLiu Zhi-JieHua TianMu YuHu ZhianYuan PengZhang Zhe - G-protein coupled receptor 139 (GPR139) has been detected in the medial septum (MS) cholinergic neuron, but its roles in cholinergic circuits associated with Alzheimer's disease (AD) remain unclear. Using a variety of experimental approaches, including the establishment of AD mouse models, viral injection, immunohistochemistry, ELISA, TUNEL apoptosis assay, Golgi staining, electrophysiological recording, fiber photometry, and behavioral tests, we found that knockdown of GPR139 in MS cholinergic neurons exacerbated early-stage cognitive decline, apoptosis, and synaptotoxicity in the basal forebrain of 6-month-old APP/PS1 mice. GPR139 activation by agonist improved memory and increased the firing and excitability of MS cholinergic neurons in ICV-Aβ mice. Strikingly, the MS provides extensive cholinergic projections to the ventral hippocampal CA3 (vCA3) subregion. Using chemogenetic approaches and 6-/9-month-old APP/PS1 mice, we further showed that inhibiting the MS→vCA3 cholinergic projection disrupted spatial temporal order memory in the early stages of AD, and activation of GPR139 improved memory deficits possibly via the MS→vCA3 cholinergic circuit in the advanced stages. These findings reveal that GPR139 in the MS→vCA3 cholinergic circuit may serve as a critical regulator of cognitive function and offer promising therapeutic strategies for AD. - Source: PubMed
Publication date: 2026/06/01
Li HuixianHou XiaoyingQin ChiLi XuyiWu XianMu Ronghao - Opioid use disorder is a chronic, relapsing condition that continues to rise worldwide. Naloxone (Narcan®), an opioid antagonist, reverses overdose but triggers strong negative affect. The neuronal circuits underlying these aversive effects remain unclear. We previously identified mu opioid receptor-expressing habenular neurons (Hb-MOR) as key encoders of negative emotional states and hypothesized that they also mediate naloxone aversion. - Source: PubMed
Publication date: 2026/05/29
Ozdemir DersuEbner ChiaraMeyer JudithPons FlorianChampagnol-Di Liberti CedricGuimaraes-Olmo IsabellaRahman Md ToufiqurDecker Ann MWendling OliviaSchwartz EricDumas SylvieEhrlich Aliza TLaverny GillesDiana Marco AJin ChunyangKieffer Brigitte LDarcq Emmanuel - G protein-coupled receptors (GPCRs) represent one of the most extensively targeted receptor families in central nervous system (CNS) pharmacology. Recent advances in GPCR biology have transformed traditional paradigms by introducing concepts such as biased signaling, allosteric modulation, and compartmentalized receptor trafficking, enabling pathway-specific therapeutic interventions. These developments have been further accelerated by emerging technologies, including high-resolution cryo-electron microscopy, biosensor platforms (e.g., BRET/FRET), human iPSC-derived models, and computational approaches such as molecular dynamics and artificial intelligence-driven drug discovery. This review provides a comprehensive overview of the evolving landscape of CNS GPCR pharmacology, integrating mechanistic insights with translational applications. Key receptor systems, including dopamine, serotonin, opioid, trace amine-associated receptor 1 (TAAR1), and GPR139, are discussed in the context of current and emerging therapeutics. In addition, advances in Class C GPCRs, including metabotropic glutamate and GABA-B receptors, are highlighted. Despite significant progress, challenges such as blood-brain barrier permeability, limited predictive biomarkers, and high attrition rates in clinical trials continue to hinder successful drug development. The convergence of receptor pharmacology, translational technologies, and precision medicine approaches offers a promising framework for overcoming these limitations. Overall, next-generation GPCR-targeted strategies hold substantial potential for developing safe, effective, and individualized therapies for CNS disorders. - Source: PubMed
Publication date: 2026/05/21
Gujjula Teja ReddyBhavya EkambaramGupta ReenaSaini PremSabitha T BKrishnamoorthy PSingh RamGopalMehta VipashaZargar Abrar Ahmad - Cervical cancer is one of the most common types of carcinomas causing morbidity and mortality in women worldwide, primarily caused by high-risk human papillomavirus (hrHPV). However, some cervical tumors, particularly adenocarcinomas, may develop independently of HPV. Chronic cervicitis, often linked to bacterial infections, increases the risk of developing squamous low and high-grade intraepithelial lesions (LSIL and HSIL, respectively) and cervical cancer. Cancer-associated inflammation activates key signaling pathways (NF-κB, STAT, and FOXO), regulating orphan G protein-coupled receptors (oGPCRs) implicated in cancer. Notably, GPR161, GPR132, GPR20, and GPR139 play roles in various tumors. This study analyzed cervical tissue samples from 45 women undergoing colposcopy at UNEME Oncology in Mexicali, Baja California. Patient data, including reproductive history and lifestyle factors, were collected. The histopathological analysis identified 31.1% with cervicitis, 40% with LSIL, and 28.8% with HSIL. mRNA expression of orphan GPRs varied among groups, with GPR132 and GPR20 significantly elevated in LSIL samples (p < 0.05), while GPR139 expression was reduced in LSIL (p < 0.05). No significant difference was found for GPR161. The differential expression of oGPCRs in cervical tissue suggests their involvement in the progression of LSIL and HSIL, offering insights into novel therapeutic targets. - Source: PubMed
Publication date: 2026/03/30
Rodríguez Jessica EGonzález-Ramírez JavierBarquet-Nieto AlinaRamírez-Rosales Gladys ECruz-Izaguirre Lilly GReyes-Solorio Brenda JCruz-Nieves Rosa PTorres-Maravilla EdgarRuiz-Hernández Armando