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Neuropeptide S receptor C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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The neuropeptide S receptor (NPS receptor) responds to the 20 amino-acid peptide neuropeptide S derived from a precursor (NPS, P0C0P6). NPS activates its receptor at low nanomolar concentrations elevating intracellular cAMP and calcium levels [21]. Currently, some peptidic and small molecule NPS receptor antagonists are available as research tools [2,9,18,22]. No NPS receptor ligands are currently used clinically.
Receptors
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NPS receptor C
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Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
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Multiple single-nucleotide polymorphisms (SNP) and several splice variants have been identified in the human NPS receptor (NPSR1). The most common of these is an Asn-Ile exchange at position 107 (Ile107Asn, rs324981). Both variants displayed similar binding affinity but NPSR Ile107 shows higher NPS potency (by approx. 10-fold) than NPSR1 Asn107 [21]. Several epidemiological studies reported an association between the Ile107Asn receptor variant and susceptibility to panic disorders [5-6,19-20]. The SNP Ile107Asn (rs324981) has also been linked to sleep behavior [8], inflammatory bowel disease [4], schizophrenia [15], increased impulsivity and ADHD symptoms [13]. Interestingly, a carboxy-terminal splice variant of human NPS receptor was found to be overexpressed in asthmatic patients [14]. Additionally, the gain-of-function variant NPSR1 Tyr206His has been described in a single family where it dramatically reduces total sleep time [28]. In preclinical animal models, NPS was found to increase arousal, reduce sleep and anxiety, enhance learning and memory, enhance extinction of conditioned fear, facilitate self-administration of addictive drugs, and attenuate feeding [11-12,16,25-26,30]. All of these effects could be blocked by NPSR1 antagonists. NPSR1 or NPS precursor knockout mice displayed mildly increased anxiety levels, impaired learning and memory, but no changes in sleep phenotypes or respiratory functions [1,7,17,29].