Abstract
Xu et al. investigated the physiological function and anatomical localization of a recently deorphanized G protein-coupled receptor (GPCR)-peptide ligand pair and obtained evidence that the peptide, which they named Neuropeptide S (NPS, for a conserved N-terminal serine), had the unusual effect of both promoting arousal and alleviating anxiety. Nanomolar concentrations of human, rat, or mouse NPS stimulated increased intracellular calcium concentrations in human embryonic kidney (HEK) 293 T and Chinese hamster ovary (CHO) cells stably transfected with the NPS GPCR, which suggests that the receptor activates Gq proteins. The authors used quantitative reverse transcription polymerase chain reaction (RT-PCR) to show that NPS and its receptor were highly expressed in brain, as well as in thyroid, salivary glands, and mammary glands. In situ hybridization for the NPS precursor, tyrosine hydroxylase, and corticotropin-releasing factor (CRF) revealed the existence of a previously unidentified pontine cluster of NPS-producing neurons between the locus coeruleus (LC, which is characterized by norepinephrine-producing neurons) and Barrington's nucleus (characterized by CRF-producing neurons). NPS receptor mRNA was found in various brain regions, including the amygdala, the thalamus, and the hypothalamus. NPS enhanced locomotor activity in mice and decreased slow wave and rapid eye movement (REM) sleep in rats (indicative of promoting arousal) when administered intraventricularly. NPS also promoted several behaviors in mice that are associated with anxiolytic activity. The authors note that excessive anxiety and sleep disruption are often associated with depression; Koob and Greenwell, noting that nicotine, too, is both activating and anxiolytic, provide context in a Preview. Y.-L. Xu, R. K. Reinscheid, S. Huitron-Resendiz, S. D. Clark, Z. Wang, S. H. Lin, F. A. Brucher, J. Zeng, N. K. Ly, S. J. Henriksen, L. de Lecea, O. Civelli, Neuropetide S: A neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43 , 487-497 (2004). [Online Journal] G. F. Koob, T. N. Greenwell, Neuropeptide S: A novel activating anxiolytic? Neuron 43 , 441-442 (2004). [Online Journal]
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