gastrin-releasing-peptide and Inflammation

Nuclear medicine techniques are becoming more important in imaging oncological and infectious diseases. For metabolic imaging of these diseases, antibody and peptide imaging are currently used. In recent years peptide imaging has become important, therefore the rationale for the use of peptide imaging is described in this article. Criteria for a successful peptide tracer are a high target specificity, a high binding affinity, a long metabolic stability and a high target-to-background ratio. Tracer internalization is also beneficial. For oncological imaging, many tracers are available, most originating from regulatory peptides, but penetrating peptides are also being developed. Peptides for imaging inflammatory and infectious diseases include regulatory peptides, antimicrobial peptides and others. In conclusion, for the imaging of oncological, imflammatory and infectious diseases, many promising peptides are being developed. The ideal peptide probe is characterized by rapid and specific target localization and binding with a high tumour-to-background ratio.

Topics: Antimicrobial Cationic Peptides; Bombesin; Cholecystokinin; Gastrin-Releasing Peptide; Glucagon-Like Peptide 1; Humans; Infections; Inflammation; Isotope Labeling; Neoplasms; Peptides; Radionuclide Imaging; Radiopharmaceuticals; Somatostatin; Vasoactive Intestinal Peptide

Gastrin-releasing peptide (GRP) is a neuropeptide that targets transmembrane-type receptors. Its role in allergic rhinitis (AR) has yet to be investigated. The present study utilized the nasal mucosa of AR model mice to examine GRP and GRP receptor (GRPR) expression levels, localization, and other factors to evaluate their role in AR pathology.. In vivo study in an animal model.. GRP and GRPR expression levels were examined in three different AR models established in BALB/c mice. In addition, a GRPR antagonist (RC-3095) was administered to AR mice to investigate its effect. The distribution of GRPR expression on mast cells in the nasal mucosa with AR was examined. Finally, we investigated the inhibitory effect of RC-3095 on allergy symptoms induced by histamine.. GRP and GRPR were highly expressed in the nasal mucosal epithelium and interstitial tissues surrounding the nasal glands in AR groups according to immunostaining. GRP and GRPR expression as determined by western blotting increased in the nasal mucosa as the degree of nasal sensitization increased. In addition, the average counts of sneezing and nasal rubbing after treatment in the AR + RC-3095 group were significantly lower than those in the AR + nasal saline group. Mast cells often colocalized with GRPR around nasal glands. Moreover, RC-3095 was effective in reducing sneezing induced by histamine.. The GRP-GRPR system is likely to be involved in allergic inflammation. This system may represent a novel therapeutic target for refractory AR.. NA. Laryngoscope, E377-E384, 2018.

Topics: Animals; Bombesin; Disease Models, Animal; Female; Gastrin-Releasing Peptide; Inflammation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Peptide Fragments; Receptors, Bombesin; Rhinitis, Allergic

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients.. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays.. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD.. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD.

Topics: Adult; Case-Control Studies; Dermatitis; Dermatitis, Atopic; Enzyme-Linked Immunosorbent Assay; Female; Gastrin-Releasing Peptide; Gene Expression Regulation; Granzymes; Humans; Inflammation; Killer Cells, Natural; Male; Middle Aged; Pruritus; Psoriasis; T-Lymphocytes, Cytotoxic

A recent study by Mishra and Hoon identified B-type natriuretic peptide (BNP) as an important peptide for itch transmission and proposed that BNP activates spinal natriuretic peptide receptor-A (NPRA) expressing neurons, which release gastrin releasing peptide (GRP) to activate GRP receptor (GRPR) expressing neurons to relay itch information from the periphery to the brain (Science 340:968-971, 2013). A central premise for the validity of this novel pathway is the absence of GRP in the dorsal root ganglion (DRG) neurons. To this end, they showed that Grp mRNA in DRG neurons is either absent or barely detectable and claimed that BNP but not GRP is a major neurotransmitter for itch in pruriceptors. They showed that NPRA immunostaining is perfectly co-localized with Grp-eGFP in the spinal cord, and a few acute pain behaviors in Nppb-/- mice were tested. They claimed that BNP is an itch-selective peptide that acts as the first station of a dedicated neuronal pathway comprising a GRP-GRPR cascade for itch. However, our studies, along with the others, do not support their claims.. We were unable to reproduce the immunostaining of BNP and NPRA as shown by Mishra and Hoon. By contrast, we were able to detect Grp mRNA in DRGs using in situ hybridization and real time RT-PCR. We show that the expression pattern of Grp mRNA is comparable to that of GRP protein in DRGs. Pharmacological and genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal BNP-induced scratching behavior. We show that BNP inhibits inflammatory pain and morphine analgesia.. Accumulating evidence demonstrates that GRP is a key neurotransmitter in pruriceptors for mediating histamine-independent itch. BNP-NPRA signaling is involved in both itch and pain and does not function upstream of the GRP-GRPR dedicated neuronal pathway. The site of BNP action in itch and pain and its relationship with GRP remain to be clarified.

Topics: Animals; Ganglia, Spinal; Gastrin-Releasing Peptide; Gene Expression Regulation; Inflammation; Male; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Pain; Pruritus; Receptors, Atrial Natriuretic Factor; Receptors, Bombesin; RNA, Messenger; Signal Transduction; Spinal Cord

Neutrophil migration to inflamed sites is crucial for both the initiation of inflammation and resolution of infection, yet these cells are involved in perpetuation of different chronic inflammatory diseases. Gastrin-releasing peptide (GRP) is a neuropeptide that acts through G protein coupled receptors (GPCRs) involved in signal transmission in both central and peripheral nervous systems. Its receptor, gastrin-releasing peptide receptor (GRPR), is expressed by various cell types, and it is overexpressed in cancer cells. RC-3095 is a selective GRPR antagonist, recently found to have antiinflammatory properties in arthritis and sepsis models. Here we demonstrate that i.p. injection of GRP attracts neutrophils in 4 h, and attraction is blocked by RC-3095. Macrophage depletion or neutralization of TNF abrogates GRP-induced neutrophil recruitment to the peritoneum. In vitro, GRP-induced neutrophil migration was dependent on PLC-β2, PI3K, ERK, p38 and independent of Gαi protein, and neutrophil migration toward synovial fluid of arthritis patients was inhibited by treatment with RC-3095. We propose that GRPR is an alternative chemotactic receptor that may play a role in the pathogenesis of inflammatory disorders.

Topics: Analysis of Variance; Animals; Bombesin; Chemotaxis; Cytokines; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gastrin-Releasing Peptide; Humans; Inflammation; Macrophages; Mice; Mice, Inbred C57BL; Monocytes; Neutrophils; Peptide Fragments; Receptors, Bombesin