Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system

Deorphanised G-protein-coupled receptors represent new and expanding targets for drug development. Neuropeptide B (NPB) and W (NPW) have recently been identified as the cognate endogenous ligands for the orphan receptor GPR7, now designated as NPBW1. NPB and NPW also bound to a second related orphan receptor, GPR8, now designated as NPBW2 that is present in humans but not rats or mice. In humans, high levels of NPW mRNA have been visualised in the substantia nigra, whereas moderate expression levels have been detected in the amygdala and hippocampus. In peripheral tissues, expression of NPW mRNA has been confirmed in the progenital system, comprising the kidney, testis, uterus, ovary and placenta, and also in stomach homogenates. Immunocytochemical, molecular biological and autoradiography techniques have revealed a discrete CNS distribution for NPBW1 in human, mouse and rat. Highest expression of NPBW1 mRNA and protein was identified in the amygdala and hypothalamic nuclei known to regulate feeding behaviour. [I-125]-NPW bound with a single high affinity to rat amygdala, KD 0.44 nM and 150 fmol mg(-1) protein. Physiological studies demonstrate that intracerebroventricular infusion of NPBW1 ligands modulates feeding behaviour, regulates the release of corticosterone, prolactin and growth hormone while also manipulating pain pathway. Mouse knockout models of the gene encoding either NPB or NPBW1 have a gender-specific phenotype, with moderate obesity evident in males but not females. Further investigation is required to elucidate the precise physiological role of NPB and NPW as neurotransmitters.