Expression and distribution patterns of Mas-related gene receptor subtypes A-H in the mouse intestine: inflammation-induced changes

Abstract Mas-related gene (Mrg) receptors constitute asubfamily of G protein-coupled receptors that are impli-cated in nociception, and are as such considered potentialtargets for pain therapies. Furthermore, some Mrgs havebeen suggested to play roles in the regulation of inflam-matory responses to non-immunological activation of mastcells and in mast cell–neuron communication. Except forMrgD, E and F, whose changed expression has beenrevealed during inflammation in the mouse intestine in ourearlier studies, information concerning the remainingcloned mouse Mrg subtypes in the gastrointestinal tractduring (patho) physiological conditions is lacking. There-fore, the present study aimed at identifying the presenceand putative function of these remaining cloned Mrg sub-types (n = 19) in the (inflamed) mouse intestine. Usingreverse transcriptase-PCR, quantitative-PCR and multipleimmunofluorescence staining with commercial and newlycustom-developed antibodies, we compared the ileum andthe related dorsal root ganglia (DRG) of non-inflamed micewith those of two models of intestinal inflammation, i.e.,intestinal schistosomiasis and 2,4,6-trinitrobenzene sul-fonic acid-induced ileitis. In the non-inflamed ileum andDRG, the majority of the Mrg subtypes examined weresparsely expressed, showing a neuron-specific expressionpattern. However, significant changes in the expressionpatterns of multiple Mrg subtypes were observed in theinflamed ileum; for instance, MrgA4, MrgB2and MrgB8were expressed in a clearly increased number of entericsensory neurons and in nerve fibers in the lamina propria,while de novo expression of MrgB10 was observed inenteric sensory neurons and in newly recruited mucosalmast cells (MMCs). The MrgB10 expressing MMCs werefound to be in close contact with nerve fibers in the laminapropria. This is the first report on the expression of allcloned Mrg receptor subtypes in the (inflamed) mouseintestine. The observed changes in the expression andcellular localization of the Mrg subtypes suggest that thesereceptors are involved in the mediation of primary afferentresponses, mast cell responses, and in neuroimmune com-munication during intestinal inflammation.Keywords Mas-related gene Intestinal inflammation Enteric neurons Mucosal mast cells Mouse ileumIntroductionMas-related gene (Mrg) receptors (Dong et al. 2001)orsensory neuron-specific receptors (SNSRs) (Lembo et al.2002) are encoded by the Mas oncogene-related genes andconstitute a subfamily of G protein-coupled receptors(GPCRs) in rodents and primates. Furthermore, Mrgreceptors have been described to be preferentially expres-sed in lectin B4? and glial cell line-derived neurotrophicfactor co-receptor c-Ret? primary afferent neurons, and to