Gastrin-releasing peptide receptor (GRPR) (GRPR)

The Gastrin-releasing peptide receptor (GRPR), also known as the bombesin receptor subtype 2 (BB2), is a G protein-coupled receptor (GPCR) that mediates the effects of gastrin-releasing peptide (GRP), a mammalian regulatory peptide (UniProt P30550). GRPR is involved in diverse physiological processes, including the stimulation of gastrointestinal hormone release, smooth muscle contraction, and the regulation of satiety and thermoregulation (NCBI Gene 2925). In pathology, GRPR is notably overexpressed in several major human cancers, including prostate, breast, and small cell lung cancer, while its expression in normal tissues is relatively limited (PubMed PMID: 30104339). This differential expression pattern has established GRPR as a significant target for theranostic applications in oncology. Therapeutic strategies primarily involve radiolabeled GRP analogs, such as NeoBOMB1 or RM2, which serve as delivery vehicles for diagnostic or therapeutic radionuclides to tumor sites (PubMed PMID: 33563703). Beyond oncology, GRPR is also investigated for its roles in inflammatory responses and neurological conditions like pruritus (itch).

Other names

Bombesin receptor subtype 2BB2BB2RGRP-RBombesin receptor 2

Drugs targeting GRPR typically function as either agonists or antagonists. Agonists trigger the Gq/11 signaling pathway, leading to phospholipase C activation and calcium mobilization. In the context of radiopharmaceuticals, both agonists and antagonists are used as vehicles to deliver radionuclides (e.g., Gallium-68 for imaging or Lutetium-177 for therapy) specifically to cells overexpressing the receptor, such as prostate or breast cancer cells.