Disease relevance of Galr2

• Galanin increases intracellular inositol phosphate levels in HEK 293 cells expressing the rat GALR2 receptor via a pertussis toxin-insensitive G-protein [1].

High impact information on Galr2

• GALR2-EGFP on the plasma membrane was internalized within 5-10 min after treatment with galanin or AR-M1896, a selective GALR2 agonist, with a dramatic reduction in plasma membrane localization and appearance in intracellular vesicles [2].
• Taken together these findings indicate that GALR2 undergoes constitutive endocytosis and recycling and that both ligand-independent and ligand-dependent internalization use the clathrin-dependent endocytic recycling pathway [2].
• GAL-R2 would appear to be expressed only in the anterior pituitary and hypothalamus [3].
• The GALR2 cDNA encoded a protein of 372 amino acids exhibiting 38% amino acid identity with rat GALR1 [4].
• VM cultures expressed GALR1, GALR2, and GALR3 receptor mRNA [5].

Biological context of Galr2

• The GALR2 amino acid sequence is 38% identical to GALR1 and is pharmacologically similar to GALR1 when expressed in COS-7 cells [6].
• The receptor, termed GALR2, was isolated from a rat hypothalamus cDNA library using a 125I-porcine galanin (125I-pGAL) binding assay [4].
• These results suggest that GALR2 receptor mediates galanin's regulation of pituitary hormone secretion and possibly food intake [1].
• In the present experiments trafficking of the galanin R1-(GALR1) and, in particular, the galanin R2 receptor (GALR2) was studied after fusion with enhanced green fluorescent protein (GALR1-EGFP and GALR2-EGFP) and transfection into PC12 cells [7].
• The open reading frame of GALR-2 is 1116 nucleotides long, encoding a protein of 372 amino acids with a theoretical molecular mass of 40.7 kD [8].

Anatomical context of Galr2

• We describe the cloning of a second galanin receptor type, GALR2, from rat hypothalamus [6].
• The rat GALR2 receptor mRNA is highly expressed in several brain regions, including hypothalamus and hippocampus as well as the anterior pituitary, with lower levels of expression detected in amygdala, and regions of cortex [1].
• GAL-R2 receptor mRNA was found in the granule cell layer in the dentate gyrus [9].
• Our findings indicate that dorsal root ganglia express by far the highest levels of GALR2 mRNA in the rat CNS [10].
• In the present study, we examined the regional and cellular distribution of GALR2 mRNA in the rat central nervous system (CNS) by in situ hybridization [10].

Associations of Galr2 with chemical compounds

• It was notable that four of six endocrine disruptors tested, i.e. nonylphenol, DBP, DCHP, and DEHP largely downregulated the levels of gene expression of galanin receptor 2 by 0.11- to 0.28-fold [11].
• Other genes tested, including vanilloid receptor-1, substance P, galanin receptor-2 and housekeeping genes did not alter [12].

Regulatory relationships of Galr2

• It is noteworthy that PACAP inhibited the expression of galanin receptor 2, whose ligand was shown to inhibit tyrosine hydroxylase activity [13].

Other interactions of Galr2

• Experiments with protein synthesis inhibition and Texas Red transferrin suggest that GALR2 is constitutively internalized [7].
• Moderate levels of GALR2 mRNA are observed in the olfactory bulb, olfactory tubercle, piriform and retrospinal cortices, hypothalamus (namely the preoptic area, arcuate nucleus, and dorsal hypothalamic area), substantia nigra pars compacta, and sensory trigeminal nucleus [10].
• We found that many neurons in the hypothalamus expressed both GALR2 mRNA and either somatostatin or tyrosine hydroxylase immunoreactivity [14].

Analytical, diagnostic and therapeutic context of Galr2

• Recent molecular cloning studies by our laboratory and others have identified the existence of a novel rat galanin receptor subtype, GALR2 [10].
• Using combined in situ hybridization immunohistochemistry we characterized the neurotransmitter and hormonal phenotype of cells expressing GALR2 mRNA in the hypothalamus and pituitary gland [15].

References