Interleukin-1β enhances the action of bradykinin in rat myenteric neurons through up-regulation of glial B1 receptor expression

Interleukin (IL)-1β and tumor necrosis factor α (TNFα) are released under pathological conditions in the gastrointestinal tract such as inflammatory bowel diseases (IBD). We examined the effects of IL-1β and TNFα on bradykinin (BK) -induced increases in the intracellular Ca2+ concentration ([Ca2+]i) and prostaglandin (PG) E2 release in neonatal rat myenteric plexus cells. BK evoked a [Ca2+]i increase in myenteric neurons and glial cells, both of which were potentiated by treatment with IL-1β but not TNFα. In both cell types, the [Ca2+]i responses to BK were abolished by D-Arg0[Hyp3, Thi5, D-Tic7, Oic8]-BK (HOE140), a B2R antagonist, but not affected by des-Arg9-HOE140, a B1R antagonist. After culture with IL-1β, however, the B1R antagonist suppressed the BK-induced [Ca2+]i increase. Only in glial cells did the B1R agonists des-Arg9-BK and BK fragment 1–8 evoke a [Ca2+]i rise in a dose-dependent manner. Real time RT-PCR and immunocytochemical analyses showed that IL-1β treatment increased expression of B1R mRNA in myenteric plexus cells and B1R protein in glial cells, respectively. Either indomethacin or an EP1 receptor antagonist suppressed the increased [Ca2+]i response to BK invoked by treatment with IL-1β. IL-1β treatment increased BK-induced PGE2 release from cultured myenteric plexus cells.These results suggest that IL-1β promotes up-regulation of B1R expression in glial cells, resulting in the potentiation of neural responses to BK through the elevation of PGE2 released from glial cells. The alteration of phenotypes of glial cells may be the cause of the changes in neural function in the enteric nervous system in IBD.