Tachykinin-1 receptor antagonism suppresses substance-P- and compound 48/80-induced mast cell activation from rat mast cells expressing functional mas-related GPCR B3

• Published in: Inflammation research 2020-03, Vol.69 (3), p.289-298
• Main Authors: Sahid, Muhammad N. A., Liu, Shuang, Mogi, Masaki, Maeyama, Kazutaka
• Format: Article
• Language: English
• Subjects: Allergology; Amino acids; Animal models; Animals; Antibiotics; Biomedical and Life Sciences; Biomedicine; Cell activation; Cell culture; Cell Degranulation - drug effects; Compound 48/80; Dermatology; Dinitrophenols; Fluorimetry; Fluorometry; G protein-coupled receptors; Gene expression; Genes; High-performance liquid chromatography; Histamine; Histamine Release - drug effects; Humans; Immunology; Inflammation; Inflammation - drug therapy; Ligands; Liquid chromatography; Male; Mast cells; Mast Cells - drug effects; Mast Cells - immunology; Mice; Nerve Tissue Proteins - metabolism; Neurokinin; Neurokinin NK1 receptors; Neurokinin-1 Receptor Antagonists - pharmacology; Neurology; Original Research Paper; p-Methoxy-N-methylphenethylamine - pharmacology; Peptides; Peritoneum; Pharmacology/Toxicology; Polymerase chain reaction; Protein Conformation; Rats; Receptors, G-Protein-Coupled - metabolism; Receptors, Neuropeptide - metabolism; Rheumatology; Serum Albumin, Bovine; Substance P - pharmacology; Tachykinin; Tachykinin receptors; Tachykinins - chemistry
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-020-01319-z

Objective Mice and rats are important animal models for mast cell (MC) study. However, rat Mas-related-GPCR-B3 receptor (MRGPRB3) has been less studied than its mouse counterpart. Therefore, we aimed to characterize rat MRGPRB3. Methods Mrgprb3 mRNA expression was assessed in peritoneal cells (RPCs) and peritoneal MCs (RPMCs) of wild-type rats, RPCs of MC-deficient rats, and RBL-2H3 cells by reverse-transcriptase polymerase chain reaction (RT-PCR). RPMCs, MRGPRX2 -transfected and non-transfected RBL-2H3 cells were activated by 15–30 min incubation with DNP-BSA, substance-P (SP), or compound-48/80. L732138 or CP96344 was used as a tachykinin/neurokinin-1-receptor antagonist. Histamine release from MCs was measured by HPLC fluorometry. Results Mrgprb3 mRNA expression was found in all cells, with the highest level in wild-type RPCs. All cells responded to DNP-BSA, but only MRGPRX2 -transfected-RBL-2H3 cells and RPMCs responded to all activators. L732138 (0.1–10 μM) and CP96344 (1–100 μM) suppressed SP (10 μM)-induced RPMC activation. L732138 inhibition was dose independent, whereas CP96344 inhibition occurred in a dose-dependent manner. Additionally, only CP96344 suppressed SP (100 μM)- and compound-48/80 (10 μg/mL)-induced RPMC activation. Conclusions RPMCs expressing functional MRGPRB3 response upon MRGPRX2 ligands to regulated MC-mediated activities. It`s provide novel insights for future pseudo-allergic studies in rodents.