Gastrin-releasing peptide: Different forms, different functions

All forms of the neuropeptide gastrin-releasing peptide (GRP) are derived from the precursor proGRP(1-125). Amidated GRP(18-27), which together with amidated GRP(1-27) was long thought to be the only biologically relevant product of the GRP gene, is involved in a multitude of physiological functions and acts as a mitogen, morphogen, and proangiogenic factor in certain cancers. Recently, GRP has been implicated in several psychiatric conditions, in the maintenance of circadian rhythm, in spinal transmission of the itch sensation, and in inflammation and wound repair. The actions of GRP are mediated by the GRP receptor. Over the last decade, nonamidated peptides derived from proGRP, such as the glycine-extended form GRP(18-28) and recombinant and synthetic fragments from proGRP(31-125), have been shown to be biologically active in a range of tissues and in cancer cell lines. While GRP18-28 acts via the GRP receptor, the identity of the receptor for proGRP31-125 and its fragments has not yet been established. Nonamidated fragments are also present in normal tissues and in various cancers. In fact, proGRP(31-98) is the most sensitive serum biomarker in patients with small cell lung cancer and is a significant predictor of poor survival in patients with advanced prostate cancer. (C) 2009 International Union of Biochemistry and Molecular Biology, Inc. Volume 35, Number 1, January/February 2009, Pages 69-75. E-mail: grahamsb@unimelb.edu.au