The recently discovered
prolactin-releasing peptide (PrRP) binds to the
PrRP receptor and is involved in endocrine regulation and energy metabolism. However, its main physiological role is currently unknown. Two biologically active
isoforms of PrRP exist: the 31 (
PrRP31) and the 20 (
PrRP20)
amino acid forms, which both contain a C-terminal Phe
amide sequence. In the present study, the
PrRP receptor was immunodetected in three rodent
tumor pituitary cell lines: GH3, AtT20 and RC-4B/C cells. The saturation binding of radioiodinated
PrRP31 to intact cells demonstrated a K(d) in the 10(-9)M range and a B(max) in the range of
tens of thousands binding sites per cell. For binding to RC-4B/C cells, both
PrRP31 and
PrRP20 competed with (125)I-PrRP31 with a similar K(i). The C-terminal analog PrRP13 showed lower binding potency compared to
PrRP31 and
PrRP20. All PrRP analogs increased the phosphorylation of MAPK/ERK1/2 (
mitogen-activated
phosphorylase/extracellular-regulated
kinase) and CREB (
cAMP response element-binding protein) in RC-4B/C cells. Additionally,
prolactin release was induced by the PrRP analogs in a dose-dependent manner in RC-4B/C cells. Finally, food intake after intracerebroventricular administration of PrRP analogs in fasted mice was followed. Both
PrRP31 and
PrRP20 decreased food intake, but PrRP13 did not show significant effect. Studies on pituitary cell lines expressing the
PrRP receptor are more physiologically relevant than those on cells transfected with the receptor. This cell type can be used as a model system for pharmacological studies searching for PrRP antagonists and stable effective PrRP agonists, as these drugs may have potential as
anti-obesity agents.