Bombesin and Gastrin-Releasing Peptide: Neuropeptides, Secretogogues, and Growth Factors

Lebacq-Verheyden, Anne-Marie; Trepel, Jane B.; Sausville, Edward A.; Battey, James F.

doi:10.1007/978-3-642-74781-6_3

Cited by 52 publications

(42 citation statements)

References 373 publications

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“…GRP, and other mammalian bombesin-like peptides (BLPs) such as neuromedin B, regulate a wide spectrum of physiological effects, including smooth muscle contraction, hormone secretion, metabolism, homeostasis and mitogenesis (Lebacq-Verheyden et al, 1990). The effects of GRP are primarily mediated through binding to its receptor, GRPR.…”

Section: Introductionmentioning

confidence: 99%

Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor

et al. 2003

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Head and neck squamous cell carcinomas (HNSCC) are characterized by upregulation of the epidermal growth factor receptor (EGFR), where EGFR serves as a potential therapeutic target. We previously reported that a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNSCC carcinogenesis. In the present study, we examined the mechanism of EGFR activation by GRP/GRPR in HNSCC proliferation. In HNSCC cells that express elevated levels of both GRPR and EGFR, we found that GRP induced rapid phosphorylation of EGFR as well as p44/42-MAPK activation. Using several EGFR-specific tyrosine kinase inhibitors and cells derived from EGFR knockout mice, we demonstrated that GRPinduced p44/42-MAPK activation was dependent upon EGFR activation. Further investigation demonstrated that cleavage of transforming growth factor-alpha (TGF-a) by matrix metalloproteinases mediated GRP-induced MAPK activation. In addition, HNSCC proliferation stimulated by GRP was eliminated upon specific inhibition of EGFR or MEK, and GRP failed to stimulate proliferation in EGFR-deficient cells. These results imply that the mitogenic effects of GRP in HNSCC are mediated by extracellular release of TGF-a and require the activation of an EGFR-dependent MEK/MAPK-dependent pathway.

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Section: Introductionmentioning

confidence: 99%

Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor

et al. 2003

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“…Mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) 1 and neuromedin B (NMB), are widely distributed in the nervous system and the gut. They regulate various physiological processes such as secretion, growth, muscle contraction, and neuromodulation through high affinity receptors (1,2).…”

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The Bombesin Receptor Subtypes Have Distinct G Protein Specificities

Jian

Sainz

Clark

et al. 1999

Journal of Biological Chemistry

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We used an in situ reconstitution assay to examine the receptor coupling to purified G protein ␣ subunits by the bombesin receptor family, including gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype 3 (BRS-3). Cells expressing GRP-R or NMB-R catalyzed the activation of squid retinal G␣ q and mouse G␣ q but not bovine retinal G␣ t or bovine brain G␣ i/o . The GRP-R-and NMB-R-catalyzed activations of G␣ q were dependent upon and enhanced by different ␤␥ dimers in the same rank order as follows: bovine brain ␤␥ > ␤ 1 ␥ 2 > > ␤ 1 ␥ 1 . Despite these qualitative similarities, GRP-R and NMB-R had distinct kinetic properties in receptor-G protein coupling. GRP-R had higher affinities for bovine brain ␤␥, ␤ 1 ␥ 1 , and ␤ 1 ␥ 2 and squid retinal G␣ q . In addition, GRP-R showed higher catalytic activity on squid G␣ q . Like GRP-R and NMB-R, BRS-3 did not catalyze GTP␥S binding to G␣ i/o or G␣ t . However, BRS-3 showed little, if any, coupling with squid G␣ q but clearly activated mouse G␣ q . GRP-R and NMB-R catalyzed GTP␥S binding to both squid and mouse G␣ q , with GRP-R activating squid G␣ q more effectively, and NMB-R also showed slight preference for squid G␣ q . These studies reveal that the structurally similar bombesin receptor subtypes, in particular BRS-3, possess distinct coupling preferences among members of the G␣ q family.Mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) 1 and neuromedin B (NMB), are widely distributed in the nervous system and the gut. They regulate various physiological processes such as secretion, growth, muscle contraction, and neuromodulation through high affinity receptors (1, 2). Three pharmacologically and structurally distinct bombesin receptor subtypes have been cloned and characterized in mammals as follows: the GRP-preferring receptor (GRP-R), the neuromedin B-preferring receptor (NMB-R), and bombesin receptor subtype 3 (BRS-3) which has a structure related to GRP-R and NMB-R but for which no high affinity, naturally occurring ligand has been identified as yet (2). Comparison of the predicted amino acid sequences (2) of the bombesin receptor subtypes shows all three to be structurally related members of the G protein-coupled receptor superfamily with pairwise sequence identity ranging from 48 to 54% (see Fig. 1). Upon agonist binding, G protein-coupled receptors activate specific heterotrimeric G proteins, which in turn regulate a variety of intracellular effectors such as adenylyl cyclase, phospholipase C, ion channels, and cGMP-phosphodiesterase (3).Heterotrimeric G proteins are composed of three polypeptides as follows: an ␣ subunit and a ␤␥ dimer that acts as a functional monomer. Ligand-activated G protein-coupled receptors catalyze the exchange of GTP for GDP bound to the G␣ subunit, resulting in dissociation of the GTP-activated ␣ subunit from both its cognate G␤␥ dimer and the receptor. The GTP-activated ␣ subunit as well as dissociated G␤␥ dimer in turn regulate intracellular effectors. At least 20 d...

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“…1 Two bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), have been identified in mammals. 1 GRP and NMB exert their function by binding to high affinity G-protein coupled receptors on the cell surface; those are the GRP-preferring receptor (GRPR) and the NMB-preferring receptor (NMBR). 2 In addition, a third subtype of mammalian bombesin receptors (BRS-3) has been cloned: however, high affinity natural ligand(s) specific to BRS-3 have not been identified yet.…”

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confidence: 99%

“…They modulate exocrine and endocrine processes, smooth muscle contraction, metabolism, homeostasis, and behavior. 1 However, the molecular basis of the diversity of biological effects of the bombesin system remains elusive. Distinct distributions of bombesin receptor subtypes in various tissues suggest independent roles of the receptors in such biological responses.…”

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Bombesin, obesity, and social behavior

Wada

Watase

et al. 1998

Mol Psychiatry

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The bombesin system has not been very well characterized in the brain. This may be due to a lack of specific antagonists or agonists or to the diversity of physiological effects of bombesin. Bombesin receptors are phylogenetically most related to endothelin receptors whose importance is well-known. Our studies on bombesin receptor knock-out mice indicate the necessity and potential fruitfulness of further efforts to examine in detail the role of bombesin in brain function.

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Bombesin and Gastrin-Releasing Peptide: Neuropeptides, Secretogogues, and Growth Factors

Cited by 52 publications

References 373 publications

Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor

Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor

The Bombesin Receptor Subtypes Have Distinct G Protein Specificities

Bombesin, obesity, and social behavior

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