Gastrin-Releasing Peptide

Abstract

During studies on tissue extracts of porcine gastric parietal and fundic areas, a peptide with potent gastrin-releasing abilities was detected and designated the gastrin-releasing peptide (GRP), based on the bioactivity used for its purification from porcine stomach and intestine. Porcine GRP was found to be composed of 27 amino acid residues and had striking C-terminal structural homology to the previously isolated amphibian skin peptides ranatensin and bombesin. The sole difference in the C-terminal 8 amino acids of bombesin and those in the GRPs isolated from mammals, fish, amphibians, and avian species is a histidine/glutamine interchange (GRP/bombesin) present at the 8th position (numbering unconventionally) from the C terminus of the peptides, with the C-terminal region being responsible for their recognized bioactivities. The pioneering work of Vittorio Erspamer and his colleagues demonstrated numerous potent effects of bombesin on mammalian gastrointestinal endocrine and exocrine secretions; subsequently, GRP was shown to possess similar activities. Although initially GRP was considered to be the mammalian counterpart to amphibian bombesin, the situation is not that simple. Elliot Spindles's studies demonstrate that (1) both GRP and bombesin are present in frogs, (2) there is a significantly greater homology between frog and human GRP prohormones than between frog GRP and bombesin prohormones, and (3) distinct GRP- and bombesin-preferring receptors are present in frogs. However, no peptide closer in structure to bombesin has been identified in mammals.