Prolactin-releasing peptide (PrRP) a bioactive peptide, was originally identified as an endogenous ligand of the orphan human G-protein coupled receptor, seven transmembrane domain receptor, GPR10 (hGR3, also called PrRP receptor). Like the majority of orphan receptors, PrRP receptor shows a low level of sequence homology with known GPCRs. Notwithstanding, a certain degree of homology has been reported to members of the neuropeptide Y (NPY) family of receptors. Neuropeptide Y is a 36- residue C-terminally amidated polypeptide hormone and neurotransmitter with the presence of an α-helix involving the 20 C-terminal residues, whereas the N-terminus part seems more flexible and is influenced by the medium environment¹. It has been recently demonstrated that the PrRP receptor may modulate neurotransmission specifically at glutamatergic synapses through the interaction with the same PDZ domain proteins that interact with AMPA receptors².

Binding of PrRP to the receptor results in activation of extracellular signal-related kinase (ERK) in a mainly pertussis toxin sensitive manner, suggesting coupling to G_i/o proteins.

PrRP receptor is expressed in the central nervous system with highest levels in the pituitary. Expression has also been detected in the cerebellum, brainstem, hypothalamus, thalamus, nucleus tractus solitaries, adrenal medulla and spinal cord in rat³.

PrRP is implicated in the regulation of the hypothalamic–pituitary–adrenal axis, blood pressure and nociception^4,5. Genetic studies in rodents indicate that lack of PrRP receptor leads to hyperphagia, obesity and dyslipidemia⁴. In humans, genetic variations in PrRP receptor are associated with lowered blood pressure⁵.