Neuropeptide S: Anatomy, Pharmacology, Genetics and Physiological Functions
Rainer K. Reinscheid
Program
in Pharmaceutical Sciences, Department of Pharmacology, Department of
Molecular Biology and Biochemistry, University of California Irvine,
360 Med Surge 2, Irvine, CA 92697-4625, USA rreinsch@uci.edu
Results
Probl Cell Differ (46) O. Civelli, Q.-Y. Zhou: Orphan G Protein-Coupled
Receptors and Novel Neuropeptides DOI 10.1007/400_2007_051/Published
online: 19 January 2008 © Springer-Verlag Berlin Heidelberg 2008
Abstract
Neuropeptide
S (NPS) is one of the most recent examples of a neurotransmitter
identified by the orphan receptor strategy. Impressive progress has been
made in the short time since its identification to determine
physiological functions modulated by NPS. The anatomical distribution
of NPS and its receptor, NPSR, suggests possible functions in the
regulation of vigilance states and modulation of emotional behaviors.
Early studies provided evidence that NPS induces behavioral arousal and
promotes wakefulness by suppressing all stages of sleep. NPS was also
found to produce anxiolytic-like effects in behavioral paradigms that
measure fear or responses to novelty. Recent studies have demonstrated
that NPS can modulate energy and endocrine homeostasis. Differential
regulation of NPS and NPSR transcripts was observed after caffeine or
nicotine treatment, indicating complex interactions with adenosine and
cholinergic systems. NPS has been found co-localized with other
excitatory transmitters such as glutamate, acetylcholine, or
corticotropine-releasing factor. Activation of NPSR triggers
mobilization of intracellular Ca2+ and stimulation of cAMP synthesis,
therefore increasing cellular excitability. A functional polymorphism
in NPSR has been identified that produces a gain-of-function phenotype
by increasing agonist potency upto tenfold. Finally, a gender-specific
associationof this NPSRpolymorphismwith panic disorder was found in
male patients, indicating that the NPS systemmight be involved in
modulating anxiety responses in humans. Further studies about
interactions of the NPS system with other transmitter systems might
help to discover additional functions of NPS and define its role within
complex neural networks.
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