Neuropeptide B

NPB activates NPBWR1 (GPR7) and NPBWR2 (GPR8), which couple to Gi proteins to reduce cAMP levels and activate MAPK/ERK cascades. NPBWR1 is broadly expressed in the hypothalamus, pituitary, and limbic system, while NPBWR2 has a more restricted distribution. The brominated tryptophan at position 1 of NPB is critical for its binding affinity, with non-brominated NPB having markedly reduced potency. This post-translational modification is unique and may serve as a metabolic stability mechanism.

ICV NPB administration in rodents produces orexigenic effects when given during the light phase (rest phase for nocturnal rodents) but can reduce food intake in other contexts. The net effect depends on nutritional status, time of day, and dose. NPBWR1 knockout mice develop late-onset obesity, suggesting tonic NPB signaling suppresses weight gain over time. NPB may act as a satiety signal in some circuits while simultaneously modulating stress-driven eating.

NPB stimulates acth/" class="wiki-internal-link">ACTH and corticosterone release, activating the HPA axis. NPBWR1 is expressed on pituitary corticotrophs and hypothalamic CRH neurons, providing a pathway for NPB to regulate stress responses. This overlap of feeding and stress regulation is consistent with the role of HPA activation in appetite modulation. NPB may serve as a gut-brain-HPA stress integration signal during nutritional challenges.

ICV NPB-29 stimulates feeding in satiated rats at 3-10 nmol doses. Conversely, chronic NPBWR1 agonism reduces body weight and adiposity in some paradigms. NPBWR1 knockout mice on high-fat diet develop significantly greater obesity than wild-type mice, establishing a tonic weight-suppressing role. These opposing acute and chronic effects suggest NPB operates within a complex set-point system for body weight.

ICV NPB-29 reduces thermal hyperalgesia and mechanical allodynia in rat inflammatory pain models, suggesting a supraspinal analgesic action. The mechanism may involve opioid system interactions, as naloxone partially blocks NPB analgesia. NPB also reduces anxiety-like behavior in open field and elevated plus-maze tests, connecting pain modulation with emotional state regulation.

NPB stimulates prolactin and ACTH secretion from pituitary cells in vitro. NPBWR1 is expressed on lactotrophs and corticotrophs. This neuroendocrine role positions NPB as a hypothalamic releasing factor candidate for pituitary hormones, adding to the complexity of its physiological roles beyond feeding and pain.