Neuropeptide S Receptors

Neuropeptide S receptor 1 (NPSR1) is a 7-transmembrane receptor which binds neuropeptide S. NPSR1 is expressed in the CNS and has roles in the modulation of locomotor activity, anxiety behavior and food intake, as well as in innate immunity in the periphery.


Neuropeptide S Receptors Agonists

Cat. No. Product Name / Activity
5857 Neuropeptide S (Mouse)
Endogenous Neuropeptide S receptor agonist

Neuropeptide S Receptors Antagonists

Cat. No. Product Name / Activity
5161 ML 154
Potent Neuropeptide S receptor antagonist
4510 SHA 68
Selective Neuropeptide S receptor antagonist

Neuropeptide S receptor 1 (NPSR1/GPR154) is a G-protein coupled receptor for neuropeptide S (NPS). It is coded for by the NPSR1 gene and has three isoforms that contain seven transmembrane domains, as well as non-functional isoforms which do not show membrane expression. NPSR1 is widely expressed throughout the central nervous system, indicating its involvement in multiple neurophysiological functions. In contrast, the NPS gene is only expressed in isolated cells within the amygdala, dorsomedial hypothalamic nuclei and peri-locus coeruleus, as well as the principal sensory trigeminal nucleus and lateral parabrachial nucleus of the brainstem.

NPS action at NPSR1 modulates several processes, including locomotor activity, spatial memory, anxiety behaviours and food intake. NPSR1 is reported to be coupled to both Gq and Gs G-protein α-subunits, leading to an increase in intracellular calcium levels, cAMP accumulation and cellular excitability upon binding of NPS.

In vitro and in vivo studies have revealed potential roles for NPS and its receptor in anxiety behaviours and associated memory formation. In mouse brain slices, NPS application increases glutamatergic transmission onto basolateral amygdala GABA interneurons, explaining the inhibitory effects of NPS on expression of contextual fear memories, as well as anxiolytic effects of NPS and its ability to facilitate extinction of aversive memories. In vivo, intracerebroventricular administration of NPS in rodents causes stimulation of locomotor activity, a reduction in sleeping time and increase in wakefulness, as well as anxiolytic effects in behavioral tests. Polymorphisms in the human NPSR1 gene have also been associated with panic disorders and increased sensitivity to anxiety. Additionally, NPS causes an increase in alcohol and drug seeking behaviors in animal models.

The function of NPS and its receptor is not just isolated to the CNS. Macrophages respond to NPS with reduced adhesion and increased phagocytosis and chemotaxis. Increased expression of NPSR1 has also been identified in ciliated cells of the epithelium and in bronchial smooth muscle cells in asthma, with polymorphisms in the NPSR1 gene being associated with asthma.

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