Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFPinduced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob͞ob and db͞db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate. Our findings suggest that QRFP and GPR103A͞B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.grooming ͉ hypothalamus ͉ QRFP ͉ wakefulness ͉ metabolic syndrome G protein-coupled receptors (GPCRs) are members of a large protein family that share common structural motifs, including seven transmembrane helices, and play pivotal roles in cell-to-cell communications and in the regulation of cell functions. A large number of GPCRs still remain as ''orphan receptors'' whose cognate ligands have yet to be identified. Identification of ligands for orphan GPCRs provides a basis for understanding the physiological roles of those GPCRs and their ligands, which can involve the central nervous, endocrine, reproductive, cardiovascular, immune, inflammatory, digestive, and metabolic systems.GPR103 (also referred to as SP9155 or AQ27) is an orphan GPCR that shows similarities with orexin, neuropeptide FF, and cholecystokinin receptors. Its mRNA has been detected predominantly in the brain including the cerebral cortex, pituitary, thalamus, hypothalamus, basal forebrain, midbrain, and pons in humans (1). Through bioinformatics approaches, two groups reported putative ligands for GPR103 as a part of a directed effort to identify the precursor genes for a novel RF-amide peptide and its receptor (2, 3). They identified a gene encoding a preproprotein that can be processed into several potential peptides, including a 26-aa (termed P518) and a 43-aa RF-amide peptide (termed QRFP) (2, 3). Both of these peptides activate GPR103, but the 43-aa QRFP exhibited more potent agonistic activity. When intravenously injected into rats, QRFP (43-aa) stimulates aldosterone release (3). The 26-aa RF-amide peptide (termed 26RFa) was independently purified from frog brain by monitoring NPFF-like immunoreactivity (4), and it exhibits orexigenic act...

Background:The demand of a burr hole surgery for chronic subdural hematoma (CSDH) is increasing in the global aging society. Burr hole-derived autologous bone dusts are not associated with extra costs compared with other commonly used synthetic materials. In addition, postoperative calvarium ossification requires periosteum-mediated blood supply, which is lacking after using avascular synthetic materials. Based on these findings, we hypothesized that the combination of the bone plugs and the preserved periosteum during burr hole surgeries for CSDH would induce efficient calvarium ossification.Methods:We evaluated the long-term effects of bone plugs on the degree of ossification and cosmetic appearance of the skin covering the burr hole sites. We included 8 patients (9 burr holes) who received the autologous bone dust derived from burr holes. As the control group, 9 burr holes that did not receive any burr hole plugs were retrospectively selected. These burr holes were evaluated by computed tomography (CT) scan for the calvarium defect ratios, CT value-based ossification, and the degree of skin sinking.Results:Ossification was observed in all the bone plugs by the bone density CT scans; they maintained their volume at 12 months after the surgeries. The calvarium defect ratios (volume ratios of the unossified parts in the burr holes) gradually increased during the first 6 months and reached 0.44 at 12 months. The mean CT values also increased from 527 HU to 750 HU for the first 6 months and reached 905 HU at 12 months. The degrees of skin sinking at the burr hole sites with the bone plugs were 1.24 mm whereas those without the bone plugs were 2.69 mm (P = 0.004).Conclusion:Application of burr hole-derived autologous bone dust is associated with better ossification and objective cosmetic result following burr hole surgery after CSDH.

CCA, common carotid arteryECA, external carotid arteryICA, internal carotid arteryPTA, percutaneous transluminal angioplasty.

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Urgent CAS for carotid-related SIE with hemodynamic impairment appears to be an effective method for achieving good clinical outcomes.