Neuropeptide S is a neuropeptide

Neuropeptide

Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...

 found in human and mammalian brain

Brain

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

, mainly produced by neurons in the amygdala

Amygdala

The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...

 and between Barrington's nucleus

Pontine micturition center

The Pontine micturition center is a collection of cell bodies located in the rostral pons in the brainstem that is involved in the supraspinal regulation of micturition . The PMC makes connections with other brain centers to control micturition, including the hypothalamus, the cerebral cortex and...

 and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas. NPS binds specifically to a newly de-orphaned G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

, NPSR

Neuropeptide S receptor

The neuropeptide S receptor is a member of the G-protein coupled receptor superfamily of integral membrane proteins which binds neuropeptide S...

. Animal studies show that NPS suppresses anxiety

Anxiety

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

 and appetite

Appetite

The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear. It has also been shown to significantly enhance dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 activity in the mesolimbic pathway

Mesolimbic pathway

The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...

.

Synthetic ligands

The non-peptide NPS receptor antagonist SHA-68

SHA-68

SHA-68 is a drug which acts as a selective, non-peptide antagonist at the neuropeptide S receptor NPSR. In animal studies it has anxiogenic effects, and blocks the stimulant action of neuropeptide S....

 blocks the effects of NPS in animals and is anxiogenic

Anxiogenic

An anxiogenic substance is one that causes anxiety. Anxiogenic effects can be measured by, for example, the hole-board test in rats and mice. A number of agents are used to provoke anxiety or panic in experimental models...

. Several peptide derived NPS agonists and antagonists have also been developed.

Peptide sequence

Below are the sequences of mature neuropeptide S in several representative species in which it is expressed:

species	sequence	MW
human	SFRNGVGTGMKKTSFQRAKS	2187.5
rat	SFRNGVGSGVKKTSFRRAKQ	2210.5
mouse	SFRNGVGSGAKKTSFRRAKQ	2182.5
dog, chimp	SFRNGVGTGMKKTSFRRAKS	2215.6
chicken	SFRNGVGSGIKKTSFRRAKS	2183.5
consensus	SFRNGVGxGXKKTSFxRAKx	N/A