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

Inflamm Res. 2020 Mar;69(3):289-298. doi: 10.1007/s00011-020-01319-z. Epub 2020 Jan 28.

Abstract

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.

Keywords: Histamine; MRGPRB3; MRGPRX2; Mast cells; Rat.

MeSH terms

  • Animals
  • Cell Degranulation / drug effects
  • Dinitrophenols
  • Histamine Release / drug effects
  • Humans
  • Inflammation / drug therapy
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neurokinin-1 Receptor Antagonists / pharmacology*
  • Protein Conformation
  • Rats
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Neuropeptide / metabolism
  • Serum Albumin, Bovine
  • Substance P / pharmacology*
  • Tachykinins / chemistry
  • p-Methoxy-N-methylphenethylamine / pharmacology*

Substances

  • Dinitrophenols
  • MRGPRX2 protein, human
  • Mrgprb2 protein, mouse
  • Mrgprb3 protein, rat
  • Nerve Tissue Proteins
  • Neurokinin-1 Receptor Antagonists
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Tachykinins
  • dinitrophenyl-bovine serum albumin
  • Serum Albumin, Bovine
  • Substance P
  • p-Methoxy-N-methylphenethylamine