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

Assessment of the bound conformation of bombesin to the BB1 and BB2 receptors DOI
Guillem Vila-Julià, J. Rubio, Juan J. Pérez

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 255, P. 127843 - 127843

Published: Nov. 11, 2023

Language: Английский

Citations

1

Stabilizing Scaffold for Short Peptides Based on Knottins DOI

Evgenii Beloborodov,

Elena Iurova,

Dmitrii Sugak

et al.

Current Cancer Drug Targets, Journal Year: 2024, Volume and Issue: 24(12), P. 1275 - 1285

Published: Feb. 15, 2024

Background: Bombesin (BBN) is a short peptide with high affinity for receptors that are expressed on the surface of various types cancer cells. However, full length BBN molecule has low in vivo stability. Objective: In our study, we propose use toxins, derived from animal and plant as scaffold molecules to enhance bioavailability stability bombesin. These peptides possess unique structure known an inhibitory cystine knot. Methods: We synthesized structures which bombesin was incorporated into domains arthropod toxins using solid-phase synthesis. The under different conditions assessed through high-performance liquid chromatography, binding cell cultures expressing receptor analyzed. Additionally, toxicity evaluated fluorescence microscopy. Results: data obtained demonstrated placing between first second cysteine residues arachnid results increased vitro bioavailability, well cytotoxicity. Conclusion: Arachnid knot can be considered increasing therapeutic peptides.

Language: Английский

Citations

0

The today and tomorrow of (almost) each itch DOI Creative Commons

Zuzanna Frydrych,

Karolina Błaszak,

Rafał Czajkowski

et al.

Forum Dermatologicum, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Itch is an unpleasant sensation on the skin that causes desire to scratch. Its aetiology can be defined by various categories such as cause, period of occurrence, location, and presence or absence disease in a given area. This burdensome symptom experience even compared chronic pain terms quality-of-life-impairment particularly common among older people. article discusses neural pathways cause itch, important but clinically challenging role histamine, some mechanisms involved itch-scratch cycle, quite novel discoveries regarding contributions gastrin-releasing peptide (GRP)/ receptor (GRPR) axis, transient potential (TRP) channels, Janus kinase. Pruritus may associated with types diseases affecting maternal-foetal relationship, skin, cholestasis, renal system mental health. Some new therapeutic options include drugs affect opioid receptors, neurokinin 1 (NK-1R) antagonists, kinase inhibitors, biologics made combining antibodies against different interleukins itch sensation. Nevertheless, finding effective form therapy for patients underlying conditions remains challenge subject ongoing clinical research.

Language: Английский

Citations

0

De novo Design of A Fusion Protein Tool for GPCR Research DOI
Kaixuan Gao, Xin Zhang, Jia Nie

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 15, 2024

Abstract G protein-coupled receptors (GPCRs) play pivotal roles in cellular signaling and represent prominent drug targets. Structural elucidation of GPCRs is crucial for discovery efforts. However, structural studies remain challenging, particularly inactive state structures, which often require extensive protein engineering. Here, we present a de novo design strategy termed “click fusion” generating fusion proteins to facilitate GPCR studies. Our method involves the rational structurally stable domains rigidly linked GPCRs. The resulting enhances thermostability target aids determining structures via cryo-electron microscopy (cryo-EM). We further demonstrate that designed can be transferred among similar with minor adjustments linker region. study introduces promising approach facilitating advancing

Language: Английский

Citations

0

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

Citations

0