galanin receptor

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is characterised by poor outcomes. Early diagnosis is essential for patient survival. The peptide galanin (GAL) and its receptors GAL1-3 are expressed in various tumours. Detailed characterisation of the GAL system in pCCA is lacking. Our study sought to characterise GAL and GAL1-3 receptor (GAL1-3 -R) expression in the healthy human bile duct, in cholestasis and pCCA. METHODS: Immunohistochemical staining was performed in healthy controls ( n = 5) and in the peritumoural tissues (with and without cholestasis) ( n = 20) and tumour tissues of pCCA patients ( n = 33) using validated antibodies...

Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS...

Galanin receptor subtypes GAL1 , GAL2 , and GAL3 are involved in several biological functions. We hypothesized that 1) GAL3 receptor activation contributes to sweating but limits cutaneous vasodilation induced by whole-body and local heating without a contribution of GAL2 ; and 2) GAL1 receptor activation attenuates both sweating and cutaneous vasodilation during whole-body heating. Young adults underwent whole-body (n = 12, 6 females) and local (n = 10, 4 females) heating. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC; ratio of laser-Doppler blood flow to mean arterial pressure) were assessed during whole-body heating (water-perfusion suit circulated with warm (35 °C) water), while CVC was also assessed by local forearm heating (33 °C-39 °C and elevated to 42 °C thereafter; each level of heating maintained for ∼30 min)...

OBJECTIVES: To analyse potential biomarkers for vibration-induced nerve damage in a population-based, observational study. DESIGN: Prospective cohort study. SETTING: Malmö Diet Cancer Study (MDCS), Malmö, Sweden. PARTICIPANTS: In a subcohort of 3898 individuals (recruited 1991-1996) from MDCS (baseline examination in 28 449 individuals; collection of fasting blood samples in a cardiovascular subcohort of MDCS of 5540 subjects), neuropathy-relevant plasma biomarkers were analysed during follow-up after filling out questionnaires, including a question whether work involved hand-held vibrating tools, graded as 'not at all', 'some' or 'much'...

Galanin is a 30 amino acid peptide that stimulates three subtype receptors (GAL1-3 R). M89b is a lanthionine-stabilized, C-terminally truncated galanin analog that specifically stimulates GAL2 R. We investigated the potential of M89b as a therapeutic for pancreatic ductal adenocarcinoma (PDAC) and assessed its safety. The anti-tumor activity of subcutaneously injected M89b on the growth of patient-derived xenografts of PDAC (PDAC-PDX) in mice was investigated. In addition, the safety of M89b was assessed in vitro using a multi-target panel to measure the off-target binding and modulation of enzyme activities...

The aim of this work was to elucidate the role of GalR2 receptor activation in protecting the rat heart in vivo from I/R damage by a pharmacological peptide agonist WTLNSAGYLLGPβAH-OH (G1) and full-length rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2 (G2) using M871, a selective inhibitor of GalR2. The peptides were prepared by the automatic solid phase synthesis using the Fmoc-strategy and purified by HPLC. 40-minute LAD coronary artery occlusion followed by a 60-minute reperfusion was performed. The criteria for damage/protection of the heart were the infarct size (IS) and plasma activity of CK-MB at the end of reperfusion...

Severe sleep deprivation (SD) has been highly associated with systemic energy wasting, such as lipid loss and glycogen depletion. Despite immune dysregulation and neurotoxicity observed in SD animals, whether and how the gut-secreted hormones participate in SD-induced disruption of energy homeostasis remains largely unknown. Using Drosophila as a conserved model organism, we characterize that production of intestinal Allatostatin A (AstA), a major gut-peptide hormone, is robustly increased in adult flies bearing severe SD...

BACKGROUND: The activation of P2Y14 receptor (P2Y14 R) promotes osteoclast formation and causes neuropathic pain, exhibiting possible link to osteoarthritis (OA). Given lack of P2Y14 R antagonist, the present study aims to search a novel P2Y14 R antagonist with low toxicity and high activity from natural products as a possible drug candidate in treatment of OA. METHODS: The role of P2Y14 R on OA was verified using P2Y14 R knockout (KO) rats. Molecular docking virtual screening strategy and activity test in P2Y14 R stably-expressed HEK293 cells were used to screen target compound from natural product library...

(R,S)-methadone ((R,S)-MTD) is a racemic µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers used for the treatment of opioid use disorder (OUD) and pain. (R)-MTD is used as an OUD treatment, has high MOR potency, and is believed to mediate (R,S)-MTD's therapeutic efficacy. (S)-MTD is in clinical development as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. In opposition to this purported mechanism of action, we found that (S)-MTD does not occupy NMDARs in vivo in rats...

Spexin, also identified as neuropeptide Q (NPQ), is a 14 amino acid peptide discovered by bioinformatic methods. It has a conserved structure in many species and is widely expressed in the central nervous system and peripheral tissues. It has an associated receptor, galanin receptor 2/3 (GALR2/3). Mature spexin peptides can exert various functions by activating GALR2/3, such as inhibiting food intake, inhibiting lipid absorption, reducing body weight, and improving insulin resistance. Spexin is expressed in the adrenal gland, pancreas, visceral fat, and thyroid, with the highest expression in the adrenal gland, followed by the pancreas...

This is a review of my laboratory's interest in status epilepticus (SE), which spanned five decades. It started with a study of the role of brain mRNAs in memory, and with the use of electroconvulsive seizures to disrupt recently acquired memories. This led to biochemical studies of brain metabolism during seizures, and to the serendipitous development of the first model of self-sustaining SE. The profound inhibition of brain protein synthesis by seizures had implications for brain development, and we showed that severe seizures and SE in the absence of hypoxemia and other metabolic complications can disrupt brain and behavioral development, a concept that was not widely accepted at that time...

Spexin2 ( SPX2 ), a paralog of SPX1 , is a newly identified gene in non-mammalian vertebrates. Limited studies in fish have evidenced its important role in food intake and energy balance modulation. However, little is known about its biological functions in birds. Using the chicken (c-) as a model, we cloned the full-length cDNA of SPX2 by using RACE-PCR. It is 1189 base pair (bp) in length and predicted to generate a protein of 75 amino acids that contains a 14 amino acids mature peptide. Tissue distribution analysis showed that cSPX2 transcripts were detected in a wide array of tissues, with abundant expression in the pituitary, testis, and adrenal gland...

The neuropeptide galanin receptor 3 (GALR3) is a class A G protein-coupled receptor (GPCR) broadly expressed in the nervous system, including the retina. GALR3 is involved in the modulation of immune and inflammatory responses. Tight control of these processes is critical for maintaining homeostasis in the retina and is required to sustain vision. Here, we investigated the role of GALR3 in retina pathologies triggered by bright light and P23H mutation in the rhodopsin (RHO) gene, associated with the activation of oxidative stress and inflammatory responses...

Dysregulation of adult hippocampal neurogenesis is linked to major depressive disorder (MDD), with more than 300 million people diagnosed and worsened by the COVID-19 pandemic. Accumulating evidence for neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular-, and behavioral-specific levels. The purpose of the current work was to evaluate the proliferating role of GAL2 receptor (GALR2) and Y1R agonists interaction upon intranasal infusion in the ventral hippocampus...

Neuropathic pain is a chronic and debilitating condition characterised by episodes of hyperalgesia and allodynia. It occurs following nerve damage from disease, inflammation or injury and currently impacts up to 17% of the UK population. Existing therapies lack efficacy and have deleterious side effects that can be severely limiting. Galanin receptor 2 (GalR2) is a G-protein coupled receptor (GPCR) implicated in the control and processing of painful stimuli. Within the nervous system it is expressed in key tissues involved in these actions such as dorsal root ganglia (DRG) and the dorsal horn of the spinal cord...

Galanin neuropeptide is distributed throughout the mammalian nervous system modulating a plethora of diverse physiological functions, including nociception, cognition and neuroendocrine regulation. The regulation of the galaninergic system is an interesting approach for the treatment of different diseases associated to those systems. Nevertheless, the pharmacological selectivity and activities of some galanin receptor (GalR) ligands are still in discussion and seem to depend on the dose, the receptor subtype and the second messengers to which they are coupled at different brain areas...

Extracellular adenosine 5'-triphosphate (ATP) is one of the best-known and frequently studied neurotransmitters. Its broad spectrum of biological activity is conditioned by the activation of purinergic receptors, including the P2X2 receptor. The P2X2 receptor is present in the central and peripheral nervous system of many species, including laboratory animals, domestic animals, and primates. However, the distribution of the P2X2 receptor in the nervous system of the domestic pig, a species increasingly used as an experimental model, is as yet unknown...

Galanin (GAL) is an important neurotransmitter released by the enteric nervous system (ENS) neurons located in the muscularis externa and submucosa enteric plexuses that acts by binding to GAL receptors 1, 2 and 3 (GALR1, 2 and 3). In our previous studies, the GAL immunoexpression was compared in colorectal cancer (CRC) tissue and the adjacent parts of the large intestine wall including myenteric and submucosal plexuses. Recently we have also found that expression levels of GALR1 and GALR3 proteins are elevated in CRC tissue as compared with their expression in epithelial cells of unchanged mucosa...

Following an unprecedented rise in the number of the aged, the incidence of age-related diseases, such as diabetes and cardiovascular disease, is consequently increasing in the world. Type 2 diabetes mellitus (T2DM) is associated with excess cardiovascular morbidity and mortality. The diabetic heart is characterized by increased cardiomyocyte stiffness and fibrotic changes. Despite many factors resulting in cardiomyocyte injury and dysfunction in diabetes, insulin resistance is still a critical etiology of diabetic cardiomyopathy...

Spexin (SPX) is a conservative tetradecapeptide which has been proven to participate in multiple physiological processes, including anxiety, feed intake, and energy metabolism in fish and mammals. However, whether SPX exists and functions in birds remain largely unknown. Using chicken (c-) as a model, the full-length cDNA encoding cSPX precursor was cloned, and it was predicted to generate a mature peptide with 14 amino acids conserved across vertebrates. The pGL4-SRE-luciferase reporter system-based functional analysis demonstrated that cSPX was effective in activating chicken galanin type Ⅱ receptor (cGALR2), cGALR2-like receptor (cGALR2L) and galanin type Ⅲ receptor (cGALR3), thus to stimulate intracellular MAPK/ERK signaling pathway...