Cloning, Expression, and Regulation of a Glucocorticoid-Induced Receptor in Rat Brain: Effect of Repetitive Amphetamine

Abstract

Behavioral sensitization to psychostimulants involves neuroadaptation of stress-responsive systems. We have identified and sequenced a glucocorticoid-induced receptor (GIR) cDNA from rat prefrontal cortex. The full-length GIR cDNA encodes a 422 amino acid protein belonging to G-protein-coupled receptor superfamily. Although the ligand for GIR is still unknown, the dendrogram construction indicates that GIR may belong to peptide receptor subfamily (e.g., substance P receptor), with more distant relationship to subfamilies of glycoprotein hormone receptors (e.g., thyrotropin receptor) and biogenic amine receptors (e.g., dopamine receptor). GIR shares 31-34% amino acid identity to the tachykinin receptors (substance P receptor, neurokinin A receptor, and neurokinin B receptor). GIR mRNA is expressed preferentially in brain, and its neuronal expression is relegated to limbic brain regions, particularly in forebrain. GIR transcript levels are increased significantly and persistently in prefrontal cortex for 7 d after discontinuation of chronic amphetamine exposure. The induction of GIR expression by amphetamine is associated with augmented behavioral activation. These findings suggest that modulation of GIR expression may be involved in behavioral sensitization, and GIR may play a role at the interface between stress and neuroadaptation to psychostimulants.

Effects of Coffee Bean Aroma on the Rat Brain Stressed by Sleep Deprivation: A Selected Transcript- and 2D Gel-Based Proteome Analysis

“…In addition, the expression level of the glucocorticoid-induced receptor gene (GIR), an orphan Gprotein-coupled receptor, of the stress with coffee group was markedly increased than that of the stress group. In that the GIR gene may be involved in mediator of anxiety and neuroendocrine control (33), the up-regulation of mRNA of GIR implies the potential anxiolytic effect of coffee bean aroma.…”

Interaction of NPY compounds with the rat glucocorticoid-induced receptor (GIR) reveals similarity to the NPY–Y2 receptor

“…The full length rat GIR cDNA (Genbank accession number AY029071 [30] was ligated into expression vector plasmid, pIRES2-EGFP using the primers (5′-CGTGAATTCGCCGCCACCAT GAATGT CCCTCCTG-3′ forward) and (5′-GATGAATTCACTCACGGCCACAGTGGGTTC-3′ reverse). COS-7 cells were transiently transfected with pIRES2-EGFP-rGIR.…”

“…Thus, NPY, PYY and their C-terminus fragments showed significant increases in GTPγ-35 S binding to rGIR, while the Y1 and Y5 selective peptides that showed poor binding to rGIR were also unable to activate GTPγ-35 S binding to rGIR (Fig 5A). Although activation with N-acetyl [Leu(28,31)] NPY [24][25][26][27][28][29][30][31][32][33][34][35][36] did not reach statistical significance, the trend for activation of GTPγ-35 S binding was evident (see Fig 5A). Exposure to increasing concentrations of PYY and NPY (3-300 nM) led to a dose dependent increase in GTPγ-35 S binding (Fig 5B), IC 50 values PYY 3-36 = 22.6 ± 0.14 nM; NPY=33.9 ± 0.08 nM).…”

“…The human GIR gene, (87% identical to mouse) also shows high levels of expression in the brain, and has been localized to chromosome 11q21 [5,20]. The rat GIR (rGIR) was cloned from prefrontal cortex in our laboratory, and was shown to be upregulated following chronic amphetamine [30]. The rat GIR elicits significant sequence identities with mouse GIR (99%) and human GIR (88%).…”

Neurobiological and Molecular Bases of Methamphetamine-Induced Behavioral Sensitization and Spontaneous Recurrence of Methamphetamine Psychosis, and its Implication in Schizophrenia

“…It was originally identified as an orphan GPCR induced by glucocorticoid and cyclic AMP in murine T-lymphocytes [115]. In situ hybridization data indicate that GIR mRNA is expressed mainly in neurons, with intense staining localized to the nucleus of the lateral olfactory tract, hippocampus, neocortex, and limbic cortical regions [116]. Interestingly, GIR mRNA expression was upregulated 1.7-fold compared with saline-treated controls in PFC after 7-day withdrawal from 5 consecutive daily amphetamine injections [116].…”