Disease relevance 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 [1].
• We conclude that the analyzed SNPs in GAL and GALR1 do not play a major role in early onset obesity or dietary fat intake in the obese children and adolescents of our study groups [2].
• We screened the coding region of GAL (including 444 bp of its promoter region) and GALR1 for mutations using single-strand conformation polymorphism analysis and denaturing HPLC in up to 191 obese children and adolescents and 106 healthy underweight young adults (students) [2].
• Expression of galanin and the GALR1 galanin receptor subtype in the colon of children with paradoxical fecal incontinence [3].
• In contrast, in vitro (125)I-labeled GAL receptor autoradiography showed substantial GAL binding in only 6 glioblastoma tissues [4].

Psychiatry related information on GALR1

• Increased galanin receptor occupancy in Alzheimer's disease [5].
• Galanin receptor antagonists : a potential novel pharmacological treatment for mood disorders [6].
• Selective galanin receptor antagonists provide a novel approach for increasing cholinergic function, as a potential adjunct to the clinical treatment of dementias [7].
• This review summarizes the mechanisms by which exogenously administered galanin may stimulate ingestion, discusses pharmacological and genetic investigations of the role of endogenous galanin on feeding and body weight, and speculates on the therapeutic potential of non-peptide galanin receptor antagonists for the treatment of appetite disorders [8].

High impact information on GALR1

• Delineation of the peptide binding site of the human galanin receptor [9].
• To determine which amino acids of the recently cloned seven-transmembrane domain-type human galanin receptor are involved in the high-affinity binding of the endogenous peptide ligand, we performed a mutagenesis study [9].
• Major challenges in this field include linking the receptor clones with each of the known physiological actions of galanin and evaluating the evidence for additional galanin receptor subtypes [10].
• We report here the isolation of a cDNA coding for a human galanin receptor from a Bowes melanoma cell line cDNA expression library, by using a radioligand binding strategy [11].
• 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 [1].

Chemical compound and disease context of GALR1

• Assuming one molecule of 125I-galanin (Mr 3,000) was bound per molecule of protein, these results suggest that the pancreatic galanin receptor is a glycoprotein with a Mr of 54,000 bearing the recognition site for the ligand and which is coupled with a pertussis toxin-sensitive G protein in the plasma membrane [12].
• Here, the cellular effects on activation of specific galanin receptor subtypes in human SH-SY5Y neuroblastoma cells were analyzed using a tetracycline-controlled expression system [13].

Biological context of GALR1

• Pharmacological characterization and tissue distribution of the human and rat GALR1 receptors [14].
• When reverse transcription (RT)-polymerase chain reaction (PCR) was used with different GALR-specific primers, only GALR2 mRNA was identified in cultured HaCaT cells and keratinocytes [15].
• The G-protein-coupled receptor, galanin receptor 1 (GALR1), maps to this region of chromosome 18q [1].
• Galanin receptor subtype GalR2 mediates apoptosis in SH-SY5Y neuroblastoma cells [13].
• This effect is best explained by the concomitant up-regulation (four- to fivefold) of GalR-1 galanin receptor transcripts induced through the activation of alpha2-adrenergic receptors [16].

Anatomical context of GALR1

• 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 [1].
• Upon competitive inhibition of GALR1, proliferation was up-regulated in immortalized and malignant keratinocytes [1].
• The presence of 5'-guanylylimidodiphosphate (GppNHp) or NaCl reduced the agonist labeling of hGALR in ENT membranes [17].
• Autoradiograms revealed intense GALR labeling, mainly in the substantia innominata, hypothalamus, the bed nucleus of the stria terminalis and within layers 2 and 4 of the ENT [17].
• These effects appear to be related to activation of GAL-R1 (ventral hippocampus) and GAL-R2 (dorsal hippocampus) receptors, respectively [18].

Associations of GALR1 with chemical compounds

• In addition, pre-treatment with guanine nucleotides may provide a more accurate measurement of GALR density since it would avoid the masking of GALRs by residual binding of endogenous GAL [5].
• Subsequent studies supported this hypothesis, showing that the effects on 5-HT release in vivo are most likely mediated by a galanin receptor in the dorsal raphe [18].
• The galanin receptor, a glycoprotein with a molecular mass of 54-60 kDa, was initially identified and characterized by radioligand binding studies with membranes prepared from tissues and cell lines [19].
• We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine [20].
• 5. Powerful inhibitory effects of galanin on the electrical (and secretory) activity of magnocellular neurons and complex presynaptic actions of galanin on the synaptic release of glutamate in the arcuate nucleus in vitro suggest an active role for multiple galanin receptor subtypes in the regulation of these hypothalamic systems in vivo [21].

Regulatory relationships of GALR1

• We previously showed that Gal1-R expression was transcriptionally regulated by the transcription factor NF-kappa B. Consistent with this transcription factor being activated in a number of inflammatory conditions, we show increased colonic Gal1-R expression in patients with colitis due to a variety of causes [22].
• Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade [23].

Other interactions of GALR1

• Discrimination of galanin receptor subtypes in RINm5F cells by structurally different galanin radioligands [24].
• The structural organization of GALNR1 suggests convergent evolution for this gene and represents a structural organization that is unique among genes encoding G-protein-coupled receptors [25].
• We have generated a model of the human GALR1 galanin receptor subtype (hGALR1) based on the alpha carbon maps of frog rhodopsin and investigated the significance of potential contact residues suggested by the model using site-directed mutagenesis [26].
• Gal1-R activation resulted in a dose-dependent increase in Cl- secretion; whereas infection of T84 cells with pathogens known to activate NF-kappa B augmented Gal1-R expression and Cl- secretion [22].
• In contrast, the effect of galanin on PRL is mediated via the pituitary-specific galanin receptor GAL-R(W), at which galanin-(3-29) is fully active [27].

Analytical, diagnostic and therapeutic context of GALR1

• Molecular modelling and site-directed mutagenesis of human GALR1 galanin receptor defines determinants of receptor subtype specificity [26].
• Molecular cloning and pharmacological characterization of a new galanin receptor subtype [28].
• Autoradiography of GALR binding was performed on human brain sections from each of the three groups [29].
• A species of approximately 70 kDa is recognized by antisera specific for hGALR1 by Western blot analysis and should allow future measurements of receptor protein expression [14].
• Identification of the CTX ADP-ribosylated G-proteins by immunoprecipitation with selective antisera indicate activation by the galanin receptor of alpha i1 and alpha i3, which have the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)) [30].

References