Function of gastrin-releasing peptide receptors in ocular itch transmission in the mouse trigeminal sensory system DOI Creative Commons
Keiko Takanami,

M. KUROIWA,

Ren Ishikawa

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Nov. 30, 2023

The prevalence of allergic conjunctivitis in itchy eyes has increased constantly worldwide owing to environmental pollution. Currently, anti-allergic and antihistaminic eye drops are used; however, there many unknown aspects about the neural circuits that transmit eyes. We focused on gastrin-releasing peptide (GRP) GRP receptor (GRPR), which reportedly involved itch transmission spinal somatosensory system, determine whether system is neurotransmission trigeminal sensory system. First, instillation mediators, such as histamine (His) non-histaminergic mediator chloroquine (CQ), exhibited concentration-dependent high levels scratching behavior, with a significant sex differences observed case His. Histological analysis revealed His CQ significantly activity GRPR-expressing neurons caudal part nucleus medulla oblongata GRPR transgenic mice. administered antagonist or bombesin-saporin ablate neurons, followed by instillation, decrease CQ-induced eye-scratching behavior toxin experiments. Intracisternal administration neuromedin C (NMC), agonist, resulted dose-dependent excessive facial despite absence an stimulus face. To our knowledge, this first study demonstrate were transmitted centrally via NMC evoked itching.

Language: Английский

Gastrin-releasing peptide in the paraventricular nucleus exerts hypertensive effects in preeclampsia DOI

Xiaomin Wang,

Md. Ahasan Ali,

Xiaoxu Liu

et al.

Neurochemistry International, Journal Year: 2025, Volume and Issue: 188, P. 106004 - 106004

Published: June 1, 2025

Language: Английский

Citations

0
Structural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3 DOI Creative Commons
Changyao Li, Youwei Xu, Wenxin Su

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114511 - 114511

Published: July 17, 2024

Bombesin receptor subtype-3 (BRS3) is an important orphan G protein-coupled that regulates energy homeostasis and insulin secretion. As a member of the bombesin (BnR) family, lack known endogenous ligands high-resolution structure has hindered understanding BRS3 signaling function. We present two cryogenic electron microscopy (cryo-EM) structures in complex with heterotrimeric

Language: Английский

Citations

3
Aurantiamide mitigates acute kidney injury by suppressing renal necroptosis and inflammation via GRPR-dependent mechanism DOI

Ruo-bing He,

Wei Li,

Rui Yao

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 139, P. 112745 - 112745

Published: July 25, 2024

Language: Английский

Citations

3
A Biomimetic C-Terminal Extension Strategy for Photocaging Amidated Neuropeptides DOI Creative Commons
Aryanna E. Layden, Xiang Ma, Caroline A. Johnson

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(36), P. 19611 - 19621

Published: Aug. 31, 2023

Photoactivatable neuropeptides offer a robust stimulus-response relationship that can drive mechanistic studies into the physiological mechanisms of neuropeptidergic transmission. The majority contain C-terminal amide, which offers potentially general site for installation caging group. Here, we report biomimetic strategy in neuropeptide C-terminus is extended via photocleavable amino acid to mimic proneuropeptides found large dense-core vesicles. We explored this approach with four prominent neuropeptides: gastrin-releasing peptide (GRP), oxytocin (OT), substance P (SP), and cholecystokinin (CCK). extension greatly reduced activity all peptides at heterologously expressed receptors. In cell type-specific electrophysiological recordings from acute brain slices, subsecond flashes ultraviolet light produced rapidly activating membrane currents activation endogenous G protein-coupled Subsequent caged CCK revealed role extracellular proteases shaping temporal dynamics signaling, striking switch-like, cell-autonomous anti-opioid effect transient signaling hippocampal parvalbumin interneurons. These results suggest linker may be photocaging amidated demonstrate how photocaged provide insights are inaccessible using conventional approaches.

Language: Английский

Citations

6
Radiopharmaceuticals Targeting Gastrin-Releasing Peptide Receptor for Diagnosis and Therapy of Prostate Cancer DOI

Yuheng Zou,

Mingxing Huang,

Mingxing Hu

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(9), P. 4199 - 4216

Published: Aug. 6, 2024

The high incidence and heavy disease burden of prostate cancer (PC) require accurate comprehensive assessment for appropriate management. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) cannot detect PSMA-negative lesions, despite its key role in PC overexpression gastrin-releasing peptide receptor (GRPR) lesions reportedly performs as a complementary target the diagnosis therapy PC. Radiopharmaceuticals derived from natural ligands GRPR have been developed. These radiopharmaceuticals enable visualization quantification within body, which can be used therapeutic guidance. Recently developed exhibit improved pharmacokinetic parameters without deterioration affinity. Several heterodimers targeting constructed alternatives because their potential to tumor with low diagnostic efficiency single detection. Moreover, some GRPR-targeted entered clinical trials initial staging or biochemical recurrence detection guide stratification therapy, indicating considerable Herein, we comprehensively summarize progress GRPR. In particular, discuss impact ligands, chelators, linkers on distribution radiopharmaceuticals. Furthermore, design scheme facilitate advancement and, thus, prompt translation.

Language: Английский

Citations

2
Interleukin-31: The Inflammatory Cytokine Connecting Pruritus and Cancer DOI Creative Commons
Sabah Akhtar, Fareed Ahmad, Majid Alam

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(9)

Published: Aug. 30, 2024

Interleukin 31 (IL-31) is a proinflammatory cytokine, mainly secreted by Type II helper T cells. It signals through heterodimeric receptor complex composed of IL-31 α and oncostatin-M β chain. The hallmark feature IL-31, in its pathological role, ability to induce pruritus mammals. Pruritus common symptom major reason morbidity cancer patients, compromising their quality life. Although, differentially expressed different tumor types could promote or inhibit progression, high expression contributing factor advanced stage severity pruritus. simultaneous existence either result from the aberrations proteins that co-exist both therapeutic treatment indirectly Although biology has predominantly been described skin diseases such as atopic dermatitis other inflammatory diseases, precise role remains elusive. Herein, we summarize current understanding on this cytokine pathogenesis cancers.

Language: Английский

Citations

2
Bombesin protects myocardium against ischemia/reperfusion injury via activation of the Keap1-Nrf2-HO-1 signaling pathway DOI
Jinyi Zhang,

Yan-Huan Du,

Zhenyu Xiong

et al.

Peptides, Journal Year: 2024, Volume and Issue: 180, P. 171279 - 171279

Published: July 23, 2024

Language: Английский

Citations

1
Synthesis and Preclinical Evaluation of a Bispecific PSMA-617/RM2 Heterodimer Targeting Prostate Cancer DOI Creative Commons
Christos Liolios,

Danai Bouziotis,

Wiebke Sihver

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(11), P. 1970 - 1978

Published: Oct. 18, 2024

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) have been used for diagnostic molecular imaging/therapy of prostate cancer (PCa). To address tumor heterogeneity, we synthesized evaluated a bispecific PSMA/GRPR ligand (3) combining PSMA-617 (1) the GRPR antagonist RM2 (2) with radiometal chelator DOTA. 3 was radiolabeled 68Ga ([68Ga]Ga-3) 177Lu ([177Lu]Lu-3). [68Ga]Ga-3 tested in following PCa cell lines affinity, time kinetic cell-binding/specificity, cell-internalization: PC-3 LNCaP. Compared to monomers (1 2), showed specific binding, similar affinities, higher lipophilicity, while its internalization rates cell-binding were superior. Docking calculations that can binding interactions inside PSMA funnel GRPR. In vivo biodistribution studies dual targeting PSMA(+) GRPR(+) tumors uptake, faster pharmacokinetic, lower kidney uptake compared 1 2

Language: Английский

Citations

1
Peptide Aptamer–Paclitaxel Conjugates for Tumor Targeted Therapy DOI Creative Commons

Xinyang Shen,

Yuan Ma,

Hang Luo

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 17(1), P. 40 - 40

Published: Dec. 30, 2024

Background/Objectives: Traditional paclitaxel therapy often results in significant side effects due to its non-specific targeting of cancer cells. Peptide aptamer–paclitaxel conjugates present a promising alternative by covalently attaching versatile peptide aptamer via linker. Compared antibody–paclitaxel conjugates, offer several advantages, including smaller size, lower immunogenicity, improved tissue penetration, and easier engineering. Methods: This review provides an in-depth analysis the multifunctional aptamers these emphasizing their structural features, therapeutic efficacy, challenges clinical applications. Results: highlights potential as novel effective approach for targeted therapy. By harnessing unique properties aptamers, demonstrate promise improving drug delivery efficiency while reducing adverse associated with traditional Conclusions: The incorporation into offers pathway developing more efficient therapies. However, further research studies are essential fully unlock innovative enhance patient outcomes.

Language: Английский

Citations

1
Bombesin receptors in GtoPdb v.2023.1 DOI Open Access

Jim Battey,

Richard V. Benya,

Robert T. Jensen

et al.

IUPHAR/BPS Guide to Pharmacology CITE, Journal Year: 2023, Volume and Issue: 2023(1)

Published: April 26, 2023

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB1, BB2, BB3 (nomenclature recommended by the NC-IUPHAR Subcommittee on receptors, [117, 4]). BB1 and BB2 are activated endogenous ligands neuromedin B (NMB), gastrin-releasing peptide (GRP), GRP-(18-27). is a tetra-decapeptide, originally derived from amphibians structurally closely related to GRP. The three Bn receptor subtypes couple primarily Gq/11 G12/13 family of G proteins [117]. Each these widely distributed in CNS peripheral tissues [80, 117, 261, 290, 248, 375, 114, 164, 165]. Activation causes wide range physiological/pathophysiogical actions, including stimulation normal neoplastic tissue growth, smooth-muscle contraction, respiration, gastrointestinal motility, feeding behavior, secretion many central nervous system effects regulation circadian rhythm, body temperature control, sighing, behavioral disorders mediation pruritus [153, 211, 255, 205, 318, 70, 35, 345, 212, 36]. an orphan receptor, although some propose it constitutively active [330]. knockout studies show has important roles glucose insulin regulation, metabolic homeostasis, feeding, temperature, obesity, diabetes mellitus growth normal/neoplastic [152, 80, 168, 224, 359, 209]. one most frequently overexpressed cancers receiving increased attention for their tumor as well tumour imaging receptor-targeted cytotoxicity [211, 288, 9, 167, 171, 172, 135, 202]. also because they primary neurotransmitters [36, 127, 318].

Language: Английский

Citations

1