Su2021 UTP Evokes CA2+ Oscillations in Human Enterochromaffin Cells via Multiple Intracellular Signaling and Ionic Mechanisms

Results: In full-thickness human ileum, anti-CdtB was specific for ICC and ganglia, based on colocalization of anti-CdtB with anti-c-kit, PGP 9.5 and S-100 (see figure). Thus antiCdtB appeared to interact with a human protein on ICCs and ganglia. Based on immunoprecipitation, a protein band was identified at 117kDa. Using mass spectroscopy this protein was identified as human vinculin. Subsequently, human vinculin was obtained commercially and by ELISA, anti-CdtB had a high affinity for human vinculin but not the control peptide. Binding to vinculin was blocked by the CdtB peptide. Conclusions: In the pathophysiology of post-infectious IBS, subjects develop antibodies to CdtB which have cross reactivity through molecular mimicry to vinculin, a cell membrane cytoskeletal protein important in neural cell migration and adherence. Given our emerging data of reduced vinculin levels in post-infectious rats and circulating anti-vinculin antibodies discriminating IBS from IBD, molecular mimicry to vinculin may be important to the cause of IBS through effects on ICC and ganglia.