Ox2

Orexin 2 receptors (OX2 R) represent a vital subtype of orexin receptors intricately involved in the regulation of wakefulness, arousal, and sleep-wake cycles. Despite their importance, there are currently no positron emission tomography (PET) tracers available for imaging the OX2 R in vivo. Herein, we report [11 C] 1 ([11 C]OX2 -2201) and [11 C] 2 ([11 C]OX2 -2202) as novel PET ligands. Both compounds 1 ( K i = 3.6 nM) and 2 ( K i = 2.2 nM) have excellent binding affinity activities toward OX2 R and target selectivity (OX2 /OX1 > 600 folds)...

The stressful experiences, by triggering a cascade of hormonal and neural changes, can produce antinociception commonly referred to as stress-induced antinociception (SIA). Orexin neuropeptides have an essential role in stress responses and pain modulation. The dentate gyrus receives orexinergic projections and has been shown to be involved in pain processing. The current study investigated the possible role of orexin-1 and orexin-2 receptors (OX1r and OX2r, respectively) within the dentate gyrus in SIA in a rat model of formalin-induced pain behavior in one hind paw...

BACKGROUND AND PURPOSE: Tau pathology contributes to a bidirectional relationship between sleep disruption and neurodegenerative disease. Tau transgenic rTg4510 mice model tauopathy symptoms including sleep/wake disturbances, which manifest as marked hyperarousal. This phenotype can be prevented by early transgene suppression, however, whether hyperarousal can be rescued after its onset is unknown. EXPERIMENTAL APPROACH: Three chronic (8-week) experiments were conducted with wild-type and rTg4510 mice after the age of onset of hyperarousal (4...

Studies establish that the brain's Orexin system is involved in pain modulation. Orexin-1 and orexin-2 receptors (OX1 and OX2r, respectively) are essential in responsiveness to stressful stimuli. Some evidence indicates that the hippocampus's dentate gyrus (DG) potentially modulates pain and stress. The present study examined the involvement of OX1 and OX2 receptors within the DG in response to acute pain after exposure to forced swim stress (FSS). Five to seven days post-stereotaxic surgery, the baseline tail-flick latency (TFL) was taken from the animal, then rats unilaterally received through an implanted cannula either different doses of OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), OX2r antagonist (TCS OX2 29; 1, 3, 10 and 30 nmol), or vehicle (0...

Long-term monitoring of volatile sulfur compounds (VSCs) released at the water-air interface from different treatment units of an anaerobic/oxic (A/O) wastewater treatment plant (WWTP) was carried out to assess the temporal and spatial emission characteristics of VSCs, to explore relationships between wastewater quality and VSC release. The VSC from non-aerated and aerated units were collected using dynamic and static chambers, respectively, and determined using gas chromatography. The VSC emission fluxes diminished in the order of primary sedimentation tank (PST) > anaerobic areas (ANA) > oxic section 1 (OX1)...

Orexin signaling in the ventral tegmental area (VTA) plays a critical role in stress and addictive behaviors. On the other hand, exposure to stress potentiates behavioral sensitization to drugs of abuse such as morphine. This study aimed to elucidate the role of orexin receptors within the VTA in restraint stress (RS)-induced morphine sensitization. Adult male albino Wistar rats underwent stereotaxic surgery, and two stainless steel guide cannulae were bilaterally implanted into the VTA. Different doses of SB334867 or TCS OX2 29 as orexin-1 (OX1) and orexin-2 (OX2) receptor antagonists were microinjected into the VTA five min before exposure to RS, respectively...

Azulene is a rare ring structure in drugs, and we investigated whether it could be used as a biphenyl mimetic in known orexin receptor agonist Nag 26, which is binding to both orexin receptors OX1 and OX2 with preference towards OX2 . The most potent azulene-based compound was identified as an OX1 orexin receptor agonist (pEC50  = 5.79 ± 0.07, maximum response = 81 ± 8% (s.e.m. of five independent experiments) of the maximum response to orexin-A in Ca2 + elevation assay)...

Insomnia is an important public health problem. The currently available treatments for insomnia can cause some adverse effects. Orexin receptors 1 (OX1 R) and 2 (OX2 R) are burgeoning targets for insomnia treatment. It is an effective approach to screening OX1 R and OX2 R antagonists from traditional Chinese medicine, which contains abundant and diverse chemical components. This study established an in-home ligand library of small-molecule compounds from medicinal plants with a definite hypnotic effect, as described in the Chinese Pharmacopoeia...

Orexins and orexinergic receptors have been shown to play a critical role in reward processing and drug addiction. Previous studies showed that the orexinergic system in the dentate gyrus (DG) region of the hippocampus affects the conditioning (acquisition) and post-conditioning (expression) phases of morphine-induced conditioned place preference (CPP). The action of each orexin receptor within the DG during conditioning and expression phases for methamphetamine (METH)-induced CPP remains unclear. The present study aimed to determine the role of orexin-1 and -2 receptors in the hippocampal DG in METH CPP acquisition and expression...

BACKGROUND: Orexins are hypothalamic neuropeptides associated with various neurophysiological activities such as sleep, arousal and reward. However, there are few studies investigating the relationships between orexin receptors (OXRs) in PVN and sexual behaviors. OBJECTIVES: To explore the roles of OXRs in PVN on sexual behaviors and uncover its potential mechanisms in males. MATERIALS AND METHODS: Orexin A, orexin 1 receptor (OX1R) antagonist SB334867, and orexin 2 receptor (OX2R) antagonist TCS-OX2-29 were microinjected into PVN to investigate the effects of OXRs on copulatory behavior testing of C57BL/6 mice...

Orexins are a family of neuropeptides that regulate various physiological events, such as sleep/wakefulness as well as emotional and feeding behavior, and that act on two G-protein-coupled receptors, i.e., orexin 1 (OX1 R) and orexin 2 receptors (OX2 R). Since the discovery that dysfunction of the orexin/OX2 R system causes the sleep disorder narcolepsy, several OX2 R-selective and OX1/2 R dual agonists have been disclosed. However, an OX1 R-selective agonist has not yet been reported, despite the importance of the biological function of OX1 R...

Orexin-A and orexin-B, also named hypocretin-1 and hypocretin-2, are two hypothalamic neuropeptides highly conserved across mammalian species. Their effects are mediated by two distinct G protein-coupled receptors, namely orexin receptor type 1 (OX1-R) and type 2 (OX2-R), which share 64% amino acid identity. Given the wide expression of OX-Rs in different central nervous system and peripheral areas and the several pathophysiological functions in which they are involved, including sleep-wake cycle regulation (mainly mediated by OX2-R), emotion, panic-like behaviors, anxiety/stress, food intake, and energy homeostasis (mainly mediated by OX1-R), both subtypes represent targets of interest for many structure-activity relationship (SAR) campaigns carried out by pharmaceutical companies and academies...

Development of high yield rice varieties is critical to ensuring global food security. However, the emission of greenhouse gases (GHG) such as Methane (CH4 ) and Nitrous oxide (N2 O) from paddy fields threatens environmental sustainability. In this study, we selected overexpressed high-affinity nitrate transporters (NRT2.3 along with their partner protein NAR2.1) cultivars, which are effective nitrogen use efficient transgenic lines pOsNAR2.1: OsNAR2.1 (Ox2) and p35S:OsNRT2.3b (O8). We used high (270 kg N/ha) and low (90 kg N/ha) nitrogen (N) fertilizers in paddy fields to evaluate morphophysiological traits, including GHG emission...

It is generally accepted that the orexin 2 receptor (OX2 R) plays a critical role in the arousal-promoting function, and in vivo imaging of OX2 R is expected to contribute to elucidation of orexin systems and the development of drugs to treat sleep disorder. In this study, we newly synthesized and characterized a radioiodinated triazole-pyrolidine derivative ([125 I]TPI) to detect OX2 R in the brain. In vitro studies using OX1 R or OX2 R expression cells showed selective binding of [125 I]TPI to OX2 R. In addition, in vitro autoradiography using rat brain sections showed high accumulation of radioactivity in the OX2 R expression region...

N,N,N ' ,N '-Tetramethylethane-1,2-diammonioacetate (L1) and N,N,N ' ,N '-tetramethylpropane-1,3-diammonioacetate (L2) are two flexible zwitterionic dicarboxylates which have been used as ligands for the uranyl ion, 12 complexes having been obtained from their coupling to diverse anions, mostly anionic polycarboxylates, or oxo, hydroxo and chlorido donors. The protonated zwitterion is a simple counterion in [H2 L1][UO2 (2,6-pydc)2 ] ( 1 ), where 2,6-pydc2- is 2,6-pyridinedicarboxylate, but it is deprotonated and coordinated in all the other complexes...

Stress suppresses the sense of pain, a physiological phenomenon known as stress-induced analgesia (SIA). Brain orexin peptides regulate many physiological functions, including wakefulness and nociception. The contribution of the orexinergic system within the nucleus accumbens (NAc) in the modulation of antinociception induced by forced swim stress (FSS) remains unclear. The present study addressed the role of intra-accumbal orexin receptors in the antinociceptive responses induced by FSS during the persistent inflammatory pain model in the rat...

In the last decade, scrub typhus, a zoonotic disease has emerged as a major health concern in Mizoram, a North-East Indian state that shares international borders with Myanmar and Bangladesh. Mizoram is a biodiversity hotspot and >85% of the state is under forest cover, which provides an ideal ecological niche for the rodents and mites to transmit scrub typhus and other rickettsial infections. Using the Weil-Felix test, a serosurvey of household rodents from 41 villages spread across all the 11 districts in Mizoram was undertaken to gather important insights on their role in disease transmission...

A novel series of 1,3,5-trioxazatriquinane with multiple effective residues (TriMER) derivatives with amino-methylene side chains was designed and synthesized based on the docking-simulation results between orexin receptors (OXRs) and TriMER-type OXR antagonists. In vitro screening against orexin receptors identified six TriMER derivatives with a cis side-chain configuration, and, among these, 20d and 28d showed full agonist activity against OX2 R at a concentration of 10 µM. To determine the absolute stereochemistry of these hit compounds, we also conducted the first asymmetric synthesis of a 1,3,5-trioxazatriquinane skeleton using a Katsuki-Sharpless asymmetric epoxidation as the key reaction and obtained a set of the individual stereoisomers...

Pacific abalone (Haliotis discus hannai) is a typical nocturnal organism. To examine the circadian expression pattern of orexin receptor type 2 (OX2 R) and its potential effect on the feeding behavior of abalone, the coding region sequence of OX2 R that is 1215 bp in length and encodes 404 amino acids was first cloned using the rapid amplification of cDNA ends technique. A recombinant expression vector was constructed for H. discus hannai based on the OX2 R protein, obtaining a recombinant protein with a molecular weight of 46 kDa...

The present study, regarding the orexin receptors having a pivotal role in reward-related psychostimulant use disorder (PUD), aimed to investigate the role of orexin-2 (OX2) receptors in the CA1 region of the hippocampus (HPC) in the extinction and reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP). In the first set of investigations, to determine the role of OX2 receptors in the extinction of METH-induced CPP, rats were daily given (during the extinction) bilaterally intra-CA1 region different doses of TCS OX2 29 (1, 3, 10, and 30 nmol/0...