Damien J Keating1, Nick J Spencer. 1. Department of Human Physiology, Flinders University, School of Medicine, South Australia, Australia.
Abstract
BACKGROUND & AIMS: The pacemaker mechanism that underlies the cyclic generation of colonic migrating motor complexes (CMMCs) is unknown, although studies have suggested that release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells in the mucosa is essential. However, no recordings of 5-HT release from the colon have been made to support these suggestions. METHODS: We used real-time amperometry to record 5-HT release directly from the mucosa in mouse isolated colon to determine whether 5-HT release from enterochromaffin cells was required for CMMC generation. RESULTS: We found that 5-HT was released from mucosal enterochromaffin cells during many, but not all, CMMC contractions. However, spontaneous CMMCs still were recorded even after removal of the mucosa, and submucosa and submucosal plexus when all release of 5-HT had been abolished. CMMC pacemaker frequency was slower in the absence of the mucosa, an effect reversed by focal application of exogenous 5-HT onto the myenteric plexus. Despite the absence of the mucosa and all detectable release of 5-HT, ondansetron significantly reduced CMMC frequency, suggesting that 5-HT(3) receptor blockade slows the CMMC pacemaker via a mechanism independent of 5-HT release from enterochromaffin cells. CONCLUSIONS: Our results show that 5-HT can be released dynamically during CMMCs. However, the intrinsic pacemaker and pattern generator underlying CMMC generation lies within the myenteric plexus and/or muscularis externa and does not require any release of 5-HT from enterochromaffin cells. Endogenous release of 5-HT from enterochromaffin cells plays a modulatory role, not an essential role, in CMMC generation.
BACKGROUND & AIMS: The pacemaker mechanism that underlies the cyclic generation of colonic migrating motor complexes (CMMCs) is unknown, although studies have suggested that release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells in the mucosa is essential. However, no recordings of 5-HT release from the colon have been made to support these suggestions. METHODS: We used real-time amperometry to record 5-HT release directly from the mucosa in mouse isolated colon to determine whether 5-HT release from enterochromaffin cells was required for CMMC generation. RESULTS: We found that 5-HT was released from mucosal enterochromaffin cells during many, but not all, CMMC contractions. However, spontaneous CMMCs still were recorded even after removal of the mucosa, and submucosa and submucosal plexus when all release of 5-HT had been abolished. CMMC pacemaker frequency was slower in the absence of the mucosa, an effect reversed by focal application of exogenous 5-HT onto the myenteric plexus. Despite the absence of the mucosa and all detectable release of 5-HT, ondansetron significantly reduced CMMC frequency, suggesting that 5-HT(3) receptor blockade slows the CMMC pacemaker via a mechanism independent of 5-HT release from enterochromaffin cells. CONCLUSIONS: Our results show that 5-HT can be released dynamically during CMMCs. However, the intrinsic pacemaker and pattern generator underlying CMMC generation lies within the myenteric plexus and/or muscularis externa and does not require any release of 5-HT from enterochromaffin cells. Endogenous release of 5-HT from enterochromaffin cells plays a modulatory role, not an essential role, in CMMC generation.
Authors: Emilie Bahne; Emily W L Sun; Richard L Young; Morten Hansen; David P Sonne; Jakob S Hansen; Ulrich Rohde; Alice P Liou; Margaret L Jackson; Dayan de Fontgalland; Philippa Rabbitt; Paul Hollington; Luigi Sposato; Steven Due; David A Wattchow; Jens F Rehfeld; Jens J Holst; Damien J Keating; Tina Vilsbøll; Filip K Knop Journal: JCI Insight Date: 2018-12-06
Authors: Dante J Heredia; Michael D Gershon; Sang Don Koh; Robert D Corrigan; Takanubu Okamoto; Terence K Smith Journal: J Physiol Date: 2013-10-14 Impact factor: 5.182
Authors: Ravinarayan Raghupathi; Michael D Duffield; Leah Zelkas; Adrian Meedeniya; Simon J H Brookes; Tiong Cheng Sia; David A Wattchow; Nick J Spencer; Damien J Keating Journal: J Physiol Date: 2013-10-07 Impact factor: 5.182