Expression of the glucocorticoid-induced receptor mRNA in rat brain

Abstract

The glucocorticoid-induced receptor (GIR) is an orphan G-protein-coupled receptor awaiting pharmacological characterization. GIR was originally identified in murine thymoma cells, and shows a widespread, yet not completely complementary distribution in mouse and human brain. Expression of the mouse GIR gene is modulated by dexamethasone in the brain and periphery, suggesting that GIR function is directly responsive to glucocorticoid signals. The rat GIR was cloned from rat prefrontal cortex by our group and was shown to be up-regulated following chronic amphetamine. The physiological role of GIR in the rat is not known at present. In order to gain a clearer understanding of the potential functions of GIR in the rat, we performed a detailed mapping of GIR mRNA expression in the rat brain. GIR mRNA showed widespread distribution in forebrain limbic and thalamic structures, and a more restricted distribution in hindbrain areas such as the spinal trigeminal nucleus and the median raphe nucleus. Areas with moderate to high levels of GIR include olfactory regions such as the nucleus of olfactory tract, hippocampus, various thalamic nuclei, cortical layers, and some hypothalamic nuclei. In comparison with previous studies, significant regional differences exist in GIR distribution in mouse and rat brain, particularly in the thalamus, striatum and in hippocampus at a cellular level. Overall, the expression of GIR in rat brain more closely approaches that seen previously in human than mouse, suggesting that rat models may be more informative for understanding the role of GIR in glucocorticoid physiology and glucocorticoid-related disease states. GIR mRNA distribution in the rat indicates a potential role of this receptor in the control of feeding and ingestive behavior, regulation of stress and emotional behavior, learning and memory, and, drug reinforcement and reward.

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

“…Within the hippocampus high expression of rGIR is found in large neurons located in proximity to the pyramidal cells [24], probably represent GABAergic interneurons [32]. NPY expression is also reported to be abundant in GABAergic interneurons and mossy fibers in the hippocampus.…”

“…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).…”

“…NPY receptors, particularly the Y 2 subtype, have been implicated in regulation of food intake, control of excitatory neurotransmission and epilepsy, circadian rhythms, learning and memory, stress-anxiety and angiogenesis [1,11,12,29]. rGIR is highly expressed in brain regions implicated in the motor as well as sensory aspects of feeding, such as various hypothalamic nuclei and hindbrain regions like the nucleus of solitary tract (NTS), dorsal motor nucleus of vagus nerve (DMX), and motor trigeminal, facial and hypoglossal nuclei [24]. Our pharmacological data supports the morphological evidence on rGIR expression in regions regulating feeding behavior.…”

“…The rat GIR elicits significant sequence identities with mouse GIR (99%) and human GIR (88%). Expression of rGIR is predominant in forebrain limbic and thalamic regions, with a more restricted distribution in hindbrain areas such as the trigeminal nucleus and median raphe nucleus [24]. GIR mRNA distribution in the rat indicates a potential role of this receptor in the control of feeding and ingestive behavior, regulation of stress and emotional behavior, learning and memory, and drug reinforcement and reward.…”

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

“…The rs116791765 locus on chr 11q21 that associated with AHI includes the G-protein receptor GPR83 (formerly Gir). Rodent studies show that this protein is expressed in multiple brain regions of relevance to OSA, including the hypoglossal nuclei, dorsal motor nucleus of vagus nerve, and the nucleus of solitary tract (36). Gpr83 down-regulation in mice leads to decreased core body temperature and increases in weight and circulating adiponectin (37).…”