Effects Of MrgC And AM Receptors On The Expression Of IL-1??nNOS Or PERK In DRG

Mas-related gene (Mrg) receptors, also known as sensory neuron-specific receptors, belong to G-protein-coupled receptors. Mrg receptors are uniquely expressed in small and medium-sized neuron in the trigeminal and dorsal root gangalia (DRG). Adrenomedullin (AM) is a member of calcitonin gene-related peptide (CGRP) family. AM has been demonstrated recently to be a pronociceptive mediator. The previous studies in our and other laboratories have shown that MrgC receptors inhibit inflammatory and neuropathic pain, and that AM receptors are involeved in the development of pathological pain in rodents. The present study examined the effects of bovine adrenal medulla peptide 8-22 (BAM8-22, a Mrg C receptor agonist) and AM22-52 (AM receptor antagonist) on lipopolysaccharide (LPS) or LPS/ATP-induced increase of IL-1?, nNOS and/or pERK in DRG in vitro. The study was aimed at investigate the mechanisms underlying these effects.The methods DRG explants cultures and Western blot were used to examine:(1) the effect of BAM8-22 on LPS-induced expression of IL-1? and nNOS; (2) the effect of AM22-52 on LPS/ATP-induced expression of IL-1? and nNOS; (3) the effect of AM22-52 on LPS/ATP-induced expression of pERK.The results showed:(1) Exposure of DRG cultures to LPS increased the expression of IL-1? and nNOS. Application of BAM8-22 inhibited LPS-induced increase of IL-1? and nNOS. However, the BAM8-22-induced inhibition disappeared in the presence of MrgC antibody.(2) Exposure of DRG cultures to LPS/ATP increased the expression of IL-1? and nNOS. Application of AM22-52 inhibited LPS-induced increase of nNOS, but not IL-1?.(3) AM22-52 inhibited LPS/ATP induced phorsphorylation of ERK signal pathway.The results in the present study suggest that the inhibition of IL-1? and nNOS is ascribed to the modulation inflammatory and neuropathic pain by MrgC receptors. On the other hand, the increase of nNOS and the activation of ERK signal pathway underly the involvement of AM receptors in the development of pathological pain.