Neuropeptide S and its receptor

Neuropeptide S (NPS) is the last neuropeptide identified via reverse pharmacology techniques. NPS selectively binds and activates a previously orphan GPCR, now named NPSR, producing intracellular calcium mobilization and stimulation of cAMP levels. Biological functions modulated by the NPS/NPSR system include anxiety, arousal, locomotion, food intake, learning and memory, pain and drug addiction. In particular, NPS evokes a unique pattern of behavioral effects: stimulation associated with anxiolysis. In the present research work, two different tools useful for the study of the NPS and its receptor have been developed: NPSR antagonists and NPSR knockout mice. The use of these generated converging evidence on the biological effects induced by the selective activation of the NPSR receptor. From these studies it is possible to foreseen that the NPS/NPSR system can represent an innovative pharmacological target for the treatment of sleep, food intake, memory disorders, anxiety states, and drug addiction.