GRP

Overview

GRP is a 27-amino acid peptide that was isolated in 1978 from porcine nonantral gastric tissue [1] and was named for its ability to stimulate gastrin release. GRP differs from... [read more] the frog tetradecapeptide, bombesin, in only one amino acid in its last 10 carboxyl-terminal residues, which is its biologically active end. For a number of years GRP was thought to be the mammalian equivalent of frog bombesin, however Xenopus laevis has been shown to produce a 29 amino acid peptide homologous to mammalian GRP, and the same frog has been shown to express different mRNAs to encode both bombesin and GRP [2,3,4]. A single human GRP-encoding gene has been described and is located on chromosome 18q21 [2,5,6]. Three different mRNA species are identified in humans generated through alternative splicing that encode precursors of slightly different chain lengths [7]. The gene comprises three exons and two introns and the second intron possesses the alternate donor site, which is used to produce the three mRNAs [8]. The human GRP mRNA encodes for a precursor of 148 amino acids that contains a signal sequence [9]. GRP_1-27 is formed by multiple enzymatic cleavages at both the amino terminus and the carboxyl terminal extended portion of the precursor. GRP_1-27 can be processed further to give GRP_10-27 [10] (which was originally termed neuromedin C) [11]. GRP is found widely, especially in the CNS and the gastrointestinal tract [12,13,14]. In the gastrointestinal tract it is found in nerve fibers and cell bodies, especially of the myenteric plexus as well as the submucosal plexus and in sympathetic prevertebral ganglia. The highest levels are found in gastric fundus, antrum and pylorus [15]. In the CNS GRP immunoreactivity is widespread in cell bodies of the cortex, pons, hypothalamus, nucleus of the solitary tract, superior olivary nucleus, nerve fibers in the thalamus, amydala, dorsal vagal nucleus and in the spinal sensory ganglia [13,14,16,17,18]. GRP has a wide range of actions, which will be briefly discussed below in the physiology and pathophysiology sections.

References

1. McDonald TJ, Jörnvall H, Nilsson G, et al. Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue. Biochem Biophys Res Commun 1979;90:227-33.
2. Spindel ER. Bombesin Peptides. Handbook of Biologically Active Peptides. 2013;None:325-330.
3. Kim JB, Johansson A, Holmgren S, et al. Gastrin-releasing peptides from Xenopus laevis: purification, characterization, and myotropic activity. Am J Physiol Regul Integr Comp Physiol 2001;281:R902-8.
4. Nagalla SR, Gibson BW, Tang D, et al. Gastrin-releasing peptide (GRP) is not mammalian bombesin. Identification and molecular cloning of a true amphibian GRP distinct from amphibian bombesin in Bombina orientalis. J Biol Chem 1992;267:6916-22.
5. Naylor SL, Sakaguchi AY, Spindel E, et al. Human gastrin-releasing peptide gene is located on chromosome 18. Somat Cell Mol Genet 1987;13:87-91.
6. Lebacq-Verheyden AM, Bertness V, Kirsch I, et al. Human gastrin-releasing peptide gene maps to chromosome band 18q21. Somat Cell Mol Genet 1987;13:81-6.
7. Battey JF, Way JM, Corjay MH, et al. Molecular cloning of the bombesin/gastrin-releasing peptide receptor from Swiss 3T3 cells. Proc Natl Acad Sci USA 1991;88:395-9.
8. Sausville EA, Lebacq-Verheyden AM, Spindel ER, et al. Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs. J Biol Chem 1986;261:2451-7.
9. Spindel ER, Chin WW, Price J, et al. Cloning and characterization of cDNAs encoding human gastrin-releasing peptide. Proc Natl Acad Sci USA 1984;81:5699-703.
10. Reeve Jr JR, Cuttitta F, Vigna SR, et al. Processing of mammalian preprogastrin-releasing peptide. Ann N Y Acad Sci 1988;547:21-9.
11. Minamino N, Kangawa K, Matsuo H. Neuromedin C: a bombesin-like peptide identified in porcine spinal cord. Biochem Biophys Res Commun 1984;119:14-20.
12. Lehmann FS, Beglinger C. Gastrin-releasing peptide. Handbook of Biologically Active Peptides. 2006;:1044-1055.
13. Jensen RT. Gastrin-releasing peptide. Encyclopedia of Gastroenterology. 2004;:179-185.
14. Ladenheim EE. Bombesin. Handbook of Biologically Active Peptides. 2013;None:1064-1070.
15. Price J, Penman E, Wass JA, et al. Bombesin-like immunoreactivity in human gastrointestinal tract. Regul Pept 1984;9:1-10.
16. Wada E, Way J, Lebacq-Verheyden AM, et al. Neuromedin B and gastrin-releasing peptide mRNAs are differentially distributed in the rat nervous system. J Neurosci 1990;10:2917-2930.
17. Battey J, Wada E. Two distinct receptor subtypes for mammalian bombesin-like peptides. Trends Neurosci 1991;14:524-8.
18. Moody TW, Merali Z. Bombesin-like peptides and associated receptors within the brain: distribution and behavioral implications. Peptides 2004;25:511-520.

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