Receptor, Galanin, Type 1
Galanin
Receptors, Galanin
Receptor, Galanin, Type 2
Receptor, Galanin, Type 3
Receptors, Gastrointestinal Hormone
Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma. (1/10)
In the United States, oral cancer accounts for more deaths annually than cervical cancer, leukemias, or Hodgkin's lymphoma. Studies have shown that aberrations of chromosome 18q develop with tumor progression and are associated with significantly decreased survival in head and neck cancer patients. The G-protein-coupled receptor, galanin receptor 1 (GALR1), maps to this region of chromosome 18q. Although the role of GALR1 has been well characterized in neuronal cells, little is known regarding this receptor in non-neuronal cells. In this study, the expression, mitogenic function, and signaling mechanism of GALR1 are investigated in normal and malignant oral epithelial cells. mRNA expression was determined via reverse transcriptase-PCR. Protein quantification was done via immunoblot analysis and enzyme-linked immunosorbent assay. For functional and signaling studies, an inhibitory antibody was generated to the N-terminal ligand binding domain of GALR1. GALR1 protein and mRNA expression and GAL secretion were detected at variable levels in immortalized human oral keratinocytes and human oropharyngeal squamous cell carcinoma cell lines. Upon competitive inhibition of GALR1, proliferation was up-regulated in immortalized and malignant keratinocytes. Furthermore, studies with the inhibitory antibody and U0126, the MAPK inhibitor, show that GALR1 inhibits proliferation in immortalized and malignant keratinocytes by inactivating the MAPK pathway. GALR1s inhibitory effects on proliferation in epithelial cells raises the possibility that inactivation or disregulation of this receptor can lead to uncontrolled proliferation and neoplastic transformation. (+info)GalR1, but not GalR2 or GalR3, levels are regulated by galanin signaling in the locus coeruleus through a cyclic AMP-dependent mechanism. (2/10)
The galanin receptors GalR1, GalR2 and GalR3 are widely expressed throughout the mouse brain and are enriched in catecholaminergic nuclei. Here, we show that GalR1 protein levels are regulated by neuronal activity and changes in cAMP levels. GalR1, but not GalR2 or GalR3, is specifically up-regulated in the LC-like Cath.a cell line in a cAMP-dependent manner. GalR1 protein and mRNA levels are also up-regulated in the LC of galanin knockout mice, whereas GalR2 and GalR3 are not. Lack of galanin-maintained cAMP tone in the galanin knockout mouse appears to result in a loss of negative feedback resulting in increased levels of CREB phosphorylation and increased GalR1 expression. These findings suggest that changes in levels of GalR1 may play an important role in modulating signaling events and neuroplasticity underlying physiological functions of the LC. (+info)Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. (3/10)
The neuropeptide galanin mediates its effects through the receptor subtypes Gal(1), Gal(2), and Gal(3) and has been implicated in anxiety- and depression-related behaviors. Nevertheless, the receptor subtypes relevant to these behaviors are not known because of the lack of available galanin-selective ligands. In this article, we use behavioral, neurochemical, and electrophysiological approaches to investigate the anxiolytic- and antidepressant-like effects of two potent small-molecule, Gal(3)-selective antagonists, SNAP 37889 and the more soluble analog SNAP 398299. Acute administration of SNAP 37889 or SNAP 398299 enhanced rat social interaction. Furthermore, acute SNAP 37889 was also shown to reduce guinea pig vocalizations after maternal separation, to attenuate stress-induced hyperthermia in mice, to increase punished drinking in rats, and to decrease immobility and increase swimming time during forced swim tests with rats. Moreover, SNAP 37889 increased the social interaction time after 14 days of treatment and maintained its antidepressant effects during forced swim tests with rats after 21 days of treatment. In microdialysis studies, SNAP 37889 partially antagonized the galanin-evoked reduction in hippocampal serotonin (5-hydroxytryptamine, 5-HT), as did the 5-HT(1A) receptor antagonist WAY100635. Their combination produced a complete reversal of the effect of galanin. SNAP 398299 partially reversed the galanin-evoked inhibition of dorsal raphe cell firing and galanin-evoked hyperpolarizing currents. These results indicate that Gal(3)-selective antagonists produce anxiolytic- and antidepressant-like effects, possibly by attenuating the inhibitory influence of galanin on 5-HT transmission at the level of the dorsal raphe nucleus. (+info)Involvement of galanin receptors 1 and 2 in the modulation of mouse vagal afferent mechanosensitivity. (4/10)
It is established that the gut peptide galanin reduces neuronal excitability via galanin receptor subtypes GALR1 and GALR3 and increases excitability via subtype GALR2. We have previously shown that galanin potently reduces mechanosensitivity in the majority of gastro-oesophageal vagal afferents, and potentiates sensitivity in a minority. These actions may have implications for therapeutic inhibition of gut afferent signalling. Here we investigated which galanin receptors are likely to mediate these effects. We performed quantitative RT-PCR on RNA from vagal (nodose) sensory ganglia, which indicated that all three GALR subtypes were expressed at similar levels. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of galanin receptor ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors which respond only to mucosal stroking. Galanin induced potent inhibition of mechanosensitivity in both types of afferents. This effect was totally lost in mice with targeted deletion of Galr1. The GALR1/2 agonist AR-M961 caused inhibition of mechanosensitivity in Galr1+/+ mice, but this was reversed to potentiation in Galr1-/- mice, indicating a minor role for GALR2 in potentiation of vagal afferents. We observed no functional evidence of GALR3 involvement, despite its expression in nodose ganglia. The current study highlights the complex actions of galanin at different receptor subtypes exhibiting parallels with the function of galanin in other systems. (+info)The effects of galanin-like peptide on energy balance, body temperature and brain activity in the mouse and rat are independent of the GALR2/3 receptor. (5/10)
Galanin-like peptide (GALP) is a neuropeptide that is thought to act on the galanin receptors GALR1, GALR2 and GALR3. In rats, i.c.v. injection of GALP has dichotomous actions on energy balance, stimulating feeding over the first hour, but reducing food intake and body weight at 24 h, as well as causing an increase in core body temperature. In mice, GALP only induces an anorexic action, and its effects on core body temperature are unknown. One aim of the present study was to determine the effects of GALP on core body temperature in mice. Intracerebroventricular injection of GALP into conscious mice had no effect on feeding over 1 h, but caused a significant reduction in food intake and body weight at 24 h. It also caused an immediate drop in core body temperature, which was followed by an increase in body temperature. To understand these different effects of GALP on energy balance in mice compared to rats, and to determine the involvement of GALR2 and GALR3, immunohistochemistry was performed to localise c-Fos, a marker of cell activation. Intracerebroventricular injection of GALP induced c-Fos expression in the parenchyma surrounding the ventricles, the ventricular ependymal cells and the meninges in mice and rats. GALP also induced c-Fos expression in the supraoptic nucleus, dorsomedial hypothalamic nucleus, lateral hypothalamus and nucleus tractus solitarius in rats but not in mice. Central administration of a GALR2/3 agonist in rats did not induce c-Fos in any of the brain regions that expressed this protein after GALP injection, and had no effect on food intake, body weight and body temperature in rats or mice. These data suggest that GALP induces differential effects on energy balance and brain activity in mice compared to rats, which are unlikely to be due to activation of the GALR2 or GALR3 receptor. (+info)Expression of mRNA for galanin, galanin-like peptide and galanin receptors 1-3 in the ovine hypothalamus and pituitary gland: effects of age and gender. (6/10)
(+info)Galanin inhibition of voltage-dependent Ca(2+) influx in rat cultured myenteric neurons is mediated by galanin receptor 1. (7/10)
(+info)Galanin negatively modulates opiate withdrawal via galanin receptor 1. (8/10)
(+info)A galanin type 1 receptor (GAL1R) is a type of G protein-coupled receptor (GPCR) that binds the neuropeptide galanin. Galanin is a naturally occurring neurotransmitter in the body that plays a role in various physiological functions, including regulation of feeding behavior, anxiety, pain perception, and memory.
The GAL1R is widely expressed throughout the central nervous system and peripheral tissues. Once galanin binds to the GAL1R, it activates a signaling cascade that can have either excitatory or inhibitory effects on neuronal activity, depending on the specific cell type and location.
The activation of GAL1R has been implicated in various pathophysiological conditions, such as pain, depression, and neurodegenerative disorders. Therefore, GAL1R is considered a potential therapeutic target for the development of new drugs to treat these conditions.
Galanin is a neuropeptide, which is a type of small protein molecule that functions as a neurotransmitter or neuromodulator in the nervous system. It is widely distributed throughout the central and peripheral nervous systems of vertebrates and plays important roles in various physiological functions, including modulation of pain perception, regulation of feeding behavior, control of circadian rhythms, and cognitive processes such as learning and memory.
Galanin is synthesized from a larger precursor protein called preprogalanin, which is cleaved into several smaller peptides, including galanin itself, galanin message-associated peptide (GMAP), and alarin. Galanin exerts its effects by binding to specific G protein-coupled receptors, known as the galanin receptor family, which includes three subtypes: GalR1, GalR2, and GalR3. These receptors are widely expressed in various tissues and organs, including the brain, spinal cord, gastrointestinal tract, pancreas, and cardiovascular system.
Galanin has been implicated in several pathological conditions, such as chronic pain, depression, anxiety, epilepsy, and neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. As a result, there is ongoing research into the development of galanin-based therapies for these conditions.
Galanin receptors are a group of G protein-coupled receptors (GPCRs) that bind to and are activated by the neuropeptide galanin. There are three subtypes of galanin receptors, named GalR1, GalR2, and GalR3, each encoded by separate genes. These receptors are widely distributed in the central and peripheral nervous systems, as well as in various endocrine organs.
Galanin receptors play important roles in modulating a variety of physiological functions, including neurotransmission, neuronal excitability, hormone release, and pain perception. Activation of these receptors can lead to either inhibitory or excitatory effects on neurons, depending on the receptor subtype and the specific cellular context.
Galanin has been implicated in several pathological conditions, such as chronic pain, epilepsy, depression, anxiety, and neurodegenerative disorders. Therefore, galanin receptors have become attractive targets for the development of novel therapeutic strategies to treat these conditions.
A galanin type 2 receptor (GAL2R) is a type of G protein-coupled receptor that binds the neuropeptide galanin. Galanin is a naturally occurring neurotransmitter and neuromodulator in the body, involved in various physiological functions such as regulation of feeding behavior, anxiety, pain perception, and memory.
The gene for the human GAL2R is called GALR2 and is located on chromosome 17. The receptor is widely expressed throughout the central nervous system, including in areas involved in reward processing, emotion regulation, and cognitive function.
Activation of the GAL2R by galanin can lead to a variety of intracellular signaling pathways, depending on the specific cell type and context. These signaling pathways can ultimately result in changes in neuronal excitability, neurotransmitter release, and gene expression.
Abnormalities in the galanin system have been implicated in several neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, depression, and chronic pain. As such, GAL2R has become a target of interest for drug development in these areas.
A "Galanin Receptor, Type 3" (GAL3R or GalR3) is a type of G protein-coupled receptor that binds the neuropeptide galanin. Galanin is a naturally occurring neurotransmitter and neuromodulator in the body that plays roles in various physiological functions, including regulation of feeding behavior, anxiety, pain perception, and memory.
GalR3 is expressed in both the central and peripheral nervous systems and has been shown to have high affinity for galanin. Activation of GalR3 can lead to a variety of intracellular signaling pathways that ultimately influence cellular responses. The specific functions of GalR3 are still being studied, but it is believed to play roles in modulating pain perception, reducing inflammation, and regulating the release of other neurotransmitters.
It's important to note that while there is a significant body of research on galanin receptors, including GalR3, much remains to be learned about their precise functions and therapeutic potential.
Gastrointestinal (GI) hormone receptors are specialized protein structures found on the surface of cells in the gastrointestinal tract. These receptors recognize and respond to specific hormones that are released by enteroendocrine cells in the GI tract. Examples of GI hormones include gastrin, secretin, cholecystokinin (CCK), motilin, and ghrelin.
When a GI hormone binds to its specific receptor, it triggers a series of intracellular signaling events that ultimately lead to changes in cell function. These changes can include increased or decreased secretion of digestive enzymes, altered motility (movement) of the GI tract, and regulation of appetite and satiety.
Abnormalities in GI hormone receptors have been implicated in a variety of gastrointestinal disorders, including functional dyspepsia, irritable bowel syndrome, and obesity. Therefore, understanding the role of these receptors in GI physiology and pathophysiology is an important area of research.