Segmental heterogeneity of electrogenic secretions in human ascending colon and rectum

Aims: We have attempted to ascertain putative segmental differences in the secretory responses of the human ascending colon and rectum. Methods: From the mucosal biopsy samples of two segments, the short-circuit current (I-sc) and tissue resistance (R-te) were compared under control conditions, as well as after the induction of secretion, using a modified Ussing chamber. We also performed semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to detect and quantify transport proteins. Results: The spontaneous I-sc in the ascending colon was found to be greater than that in the rectum (P < 0.01), whereas isobutylmethylxanthine/forskolin and carbachol (CCh) induced a greater rise in I-sc in the rectum than in the ascending colon (P < 0.05). When coupled with indomethacin pretreatment, the increase in Delta I-sc after the addition of CCh and forskolin was significant as compared to that observed without pretreatment (P < 0.05). However, in the rectum, the secretory response to CCh and forskolin was abolished to a significant degree by indomethacin (P < 0.05). Moreover, these indomethacin-induced changes were reversed by the addition of PGE2. Upon semiquantitative RT-PCR analysis, the amounts of cystic fibrosis transmembrane regulator, KCNQ1, and CLCA1 mRNAs were not found to be different between the two segments. Conclusion: There was a clear segmental heterogeneity with regard to electrogenic secretion in the human colon, and this difference can be explained by differences in the ascending colon and rectum.