Bombesin Peptides

Jensen, Robert T.; Moody, Terry W.

doi:10.1016/b978-0-12-385095-9.00069-5

Cited by 12 publications

(33 citation statements)

References 31 publications

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“…Each of these receptors is widely distributed in the CNS and peripheral tissues [625,857,1556,1642]. Activation of BB 1 and BB 2 receptors causes a wide range of physiological actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, appetite and feeding behavior, secretion and many central nervous system effects [857,858,859,1185,1317,1556]. A physiological role for the BB 3 receptor has yet to be fully defined although recently studies using receptor knockout mice and newly described agonists/antagonists suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding and other CNS behaviors and growth of normal/neoplastic tissues [625,1186,1430].…”

Section: Overviewmentioning

confidence: 99%

The Concise Guide to PHARMACOLOGY 2015/16: G protein‐coupled receptors

Alexander

Davenport

Kelly

et al. 2015

British J Pharmacology

518

249

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The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates. Conflict of interestThe authors state that there are no conflicts of interest to declare.

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Section: Overviewmentioning

confidence: 99%

The Concise Guide to PHARMACOLOGY 2015/16: G protein‐coupled receptors

Alexander

Davenport

Kelly

et al. 2015

British J Pharmacology

518

249

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“…Studies on normal and neoplastic tissues demonstrate that stimulation of BRS-3, as well as GRPR and NMBR, can result in potent stimulation of focal adhesion kinases (p125FAK, PYK-2); MAPK kinases especially ERK; EGFR; Src kinases; and paxillin[8–10,37,38,40,43,52,55–57,59]. Transactivation of the EGFR by GRPR and NMBR, has been shown to be an important signaling cascade mediating growth effects of these receptors on a number of different neoplasms including cancers of the lung (especially nonsmall cell tumors), head and neck squamous cells, neuroendocrine cells and the prostate[8,17,37,52,56–58,60–62]. Studies with BRS-3 in this area are more limited, although recently a number of studies of BRS-3 growth stimulatory effects in lung cancer cells report a similar mechanism with its growth stimulatory effects occurring primarily via EGFR transactivation[53,57].…”

Section: Brs-3 and The Mammalian Bnr Family (Table 1)mentioning

confidence: 99%

“…Studies with BRS-3 in this area are more limited, although recently a number of studies of BRS-3 growth stimulatory effects in lung cancer cells report a similar mechanism with its growth stimulatory effects occurring primarily via EGFR transactivation[53,57]. In a number of studies the transactivation of EGFR by BRS-3 and the other mammalian BnRs has been shown to involve activation of phospholipase C, Src kinases, stimulation of matrix metalloproteinases and shedding of EGF-related ligands, as well as the stimulation of reactive oxygen species[8,9,17,52,54,57]. …”

Section: Brs-3 and The Mammalian Bnr Family (Table 1)mentioning

confidence: 99%

Bombesin receptor subtype 3 as a potential target for obesity and diabetes

González

Moreno

Jensen

2015

Expert Opinion on Therapeutic Targets

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Summary Introduction Diabetes mellitus and obesity are important health issues; increasing in prevalence, both in the US and globally. There are only limited pharmacological treatments, and although bariatric surgery is effective, new effective pharmacologic treatments would be of great value. This review covers one area of increasing interest that could yield new novel treatments of obesity/diabetes mellitus. It involves recognition of the central role the G-protein-coupled receptor, bombesin receptor subtype 3(BRS-3) plays in energy/glucose metabolism. Areas covered Since the initial observation that BRS-3-knockout mice develop obesity, hypertension, impaired glucose-metabolism, and hyperphagia, there has been numerous studies of the mechanisms involved and the development of selective BRS-3-agonists/ antagonists which have marked effects on body weight, feeding, and glucose/insulin homeostasis. In this review each of these areas will be briefly reviewed. Expert opinion BRS-3 plays an important role in glucose/energy homeostasis. The development of potent, selective BRS-3 agonists demonstrates promise as a novel approach to treat obesity/diabetic states. One important question that needs to be addressed is whether BRS-3 agonists need to be centrally-acting. This is particular important in light of recent animal and human studies that report transient cardiovascular side-effects with centrally acting oral BRS-agonists.

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“…In the periphery, BRS-3 is present in pancreatic islets and BRS-3 deficient mice have increased plasma insulin [10]. Also, BRS-3 is overexpressed in a number of cancer tumors [15]. The results indicate that BRS-3 may be important in the normal and malignant CNS as well as peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth

et al. 2015

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Bombesin receptor subtype (BRS)-3 is a G protein coupled receptor (GPCR) for the bombesin (BB)-family of peptides. BRS-3 is an orphan GPCR and little is known of its physiological role due to the lack of specific agonists and antagonists. PD168368 is a nonpeptide antagonist for the neuromedin B (NMB) receptor (R) whereas PD176252 is a nonpeptide antagonist for the gastrin releasing peptide (GRP) R and NMBR but not BRS-3. Here nonpeptide analogs of PD176252 e.g. the S-enantiomer ML-18, and the R-enantiomer, EMY-98, were investigated as BRS-3 antagonists using lung cancer cells. ML-18 and EMY-98 inhibited specific 125I-BA1 (DTyr-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH2)BB6-14 binding to NCI-H1299 lung cancer cells stably transfected with BRS-3 with IC50 values of 4.8 and > 100 μM, respectively. In contrast, ML-18 bound with lower affinity to the GRPR and NMBR with IC50 values of 16 and >100 μM, respectively. ML-18 (16 μM), but not its enantiomer EMY-98, inhibited the ability of 10 nM BA1 to elevate cytosolic Ca2+ in a reversible manner using lung cancer cells loaded with FURA2-AM. ML-18 (16 μM), but not EMY-98, inhibited the ability of 100 nM BA1 to cause tyrosine phosphorylation of the EGFR and ERK in lung cancer cells. ML-18 but not EMY-98 inhibited the proliferation of lung cancer cells. The results indicate that ML-18 is a nonpeptide BRS-3 antagonist that should serve as a template to improve potency and selectivity.

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Bombesin Peptides

Cited by 12 publications

References 31 publications

The Concise Guide to PHARMACOLOGY 2015/16: G protein‐coupled receptors

The Concise Guide to PHARMACOLOGY 2015/16: G protein‐coupled receptors

Bombesin receptor subtype 3 as a potential target for obesity and diabetes

ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth

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