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Orexins-A and -B are neuropeptides derived from a single precursor prepro-orexin. The mature peptides are mainly expressed in the lateral hypothalamic and perifornical areas. The orexins have been implicated in the control of arousal and appear to be important messengers in the regulation of food intake. Two receptors for orexins have been characterised so(More)
Fractalkine is a recently identified chemokine that exhibits cell adhesion and chemoattractive properties. It represents a unique member of the chemokine superfamily because it is located predominantly in the brain in which it is expressed constitutively on specific subsets of neurons. To elucidate the possible role of neuronally expressed fractalkine in(More)
TaqMan reverse transcription polymerase chain reaction (RT-PCR) is a recently developed technique which allows the measurement of an accumulating PCR product in real time. In the present study we have validated the use of TaqMan RT-PCR for mRNA localisation studies in human and rat tissues, and for the investigation of gene expression changes in CNS animal(More)
Capsaicin, resiniferatoxin, protons or heat have been shown to activate an ion channel, termed the rat vanilloid receptor-1 (rVR1), originally isolated by expression cloning for a capsaicin sensitive phenotype. Here we describe the cloning of a human vanilloid receptor-1 (hVR1) cDNA containing a 2517 bp open reading frame that encodes a protein with 92%(More)
GABA(B) receptors are G-protein-coupled receptors that mediate the slow and prolonged synaptic actions of GABA in the CNS via the modulation of ion channels. Unusually, GABA(B) receptors form functional heterodimers composed of GABA(B1) and GABA(B2) subunits. The GABA(B1) subunit is essential for ligand binding, whereas the GABA(B2) subunit is essential for(More)
Proteins of the caspase family are involved in the signalling pathway that ultimately leads to programmed cell death (apoptosis), which has been reported to occur in some experimental models of stroke. In a previous paper we used quantitative reverse transcription and polymerase chain reaction (RT-PCR) to characterise changes in the mRNA expression of one(More)
Members of the death receptor family may play a prominent role in developmental and pathological neuronal cell death. We report the expression of the TR3 and TR7 death receptors in the adult human and rat central nervous system. Whereas expression of TR3 appears to be high in the human cerebellum, with lower levels in other brain regions, robust expression(More)
BACKGROUND Allosteric modulation of γ-secretase is an attractive therapeutic approach for the treatment of Alzheimer's disease. We recently identified a novel γ-secretase modulator, GSM-10h, which effectively lowers Aβ42 production in cells and in amyloid precursor protein transgenic mice. OBJECTIVE Here, we describe the in vivo characterization of(More)
Recently a novel subfamily of closely related orphan G protein-coupled receptors (GPCRs) was identified, called GPRC5A, GPRC5B, GPRC5C and GPRC5D. Based on sequence homology, these receptors were classified as family C GPCRs, which include metabotropic GABA(B) receptors, metabotropic glutamate receptors, the calcium sensing receptor and a number of(More)
RATIONALE Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output. Further central nervous system (CNS) roles for NmU warrant investigation.(More)