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PLoS One. 2015 Feb 25;10(2):e0117319. doi: 10.1371/journal.pone.0117319. eCollection 2015.

Neuronal expression of the human neuropeptide S receptor NPSR1 identifies NPS-induced calcium signaling pathways.

Author information

Institute of Physiology I, Neurophysiology, Westfälische Wilhelms-University Münster, Robert-Koch-Strasse, 27a, 48149, Münster, Germany.
Center of Molecular Physiology of the Brain (CMPB), Department of Neurology, University Medicine Göttingen, Waldweg, 33, 37073, Göttingen, Germany.
Institute of Experimental Pathology, ZMBE and Interdisciplinary Clinical Research Center, Westfälische Wilhelms-University Münster, Von-Esmarch-Str. 56, 48149, Münster, Germany.


The neuropeptide S (NPS) system was discovered as a novel neurotransmitter system a decade ago and has since been identified as a key player in the modulation of fear and anxiety. Genetic variations of the human NPS receptor (NPSR1) have been associated with pathologies like panic disorders. However, details on the molecular fundamentals of NPSR1 activity in neurons remained elusive. We expressed NPSR1 in primary hippocampal cultures. Using single-cell calcium imaging we found that NPSR1 stimulation induced calcium mobilization from the endoplasmic reticulum via activation of IP3 and ryanodine receptors. Store-operated calcium channels were activated in a downstream process mediating entry of extracellular calcium. We provide the first detailed analysis of NPSR1 activity and the underlying intracellular pathways with respect to calcium mobilization in neurons.

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