BACKGROUND: The migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal contractions in the interdigestive state. This study was designed to clarify the mechanisms of gastric MMC (G-MMC) and intestinal MMC (I-MMC) in conscious dogs. METHODS: Five strain gauge transducers were implanted on the stomach and intestine. To investigate the correlation between luminal 5-HT and phase III contractions, gastric and duodenal juices were collected during the MMC cycle. The 5-HT concentrations in gastric and duodenal juice were measured by HPLC. To investigate whether luminal 5-HT initiates MMC, 5-HT (10(-8)-10(-6) M, 10 ml) was administered into the duodenum 20 min after gastric phase III. To investigate the involvement of 5-HT(3) or 5-HT(4) receptors in mediating G-MMC and I-MMC, 5-HT(3) antagonists (ondansetron) or 5-HT(4) antagonists (GR 125,487) were infused for 120 min. RESULTS: Luminal administration of 5-HT (10(-6) M) initiated duodenal phase II followed by G-MMC and I-MMC with a concomitant increased release of plasma motilin. The duodenal 5-HT concentration was significantly increased during phase II (59 +/- 9 ng/ml) and phase III (251 +/- 21 ng/ml) compared to that of phase I (29 +/- 5 ng/ml). On the other hand, the 5-HT content in the stomach was not significantly changed throughout the MMC cycle. Intravenous infusion of motilin (0.3 microg/kg/h) increased the luminal 5-HT content and induced G-MMC and I-MMC. 5-HT(4) antagonists significantly inhibited both G-MMC and I-MMC, while 5-HT(3) antagonists inhibited only G-MMC. CONCLUSION: It is suggested that the MMC cycle is mediated by a positive feedback mechanism via the interaction between motilin and 5-HT.
BACKGROUND: The migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal contractions in the interdigestive state. This study was designed to clarify the mechanisms of gastric MMC (G-MMC) and intestinal MMC (I-MMC) in conscious dogs. METHODS: Five strain gauge transducers were implanted on the stomach and intestine. To investigate the correlation between luminal 5-HT and phase III contractions, gastric and duodenal juices were collected during the MMC cycle. The 5-HT concentrations in gastric and duodenal juice were measured by HPLC. To investigate whether luminal 5-HT initiates MMC, 5-HT (10(-8)-10(-6) M, 10 ml) was administered into the duodenum 20 min after gastric phase III. To investigate the involvement of 5-HT(3) or 5-HT(4) receptors in mediating G-MMC and I-MMC, 5-HT(3) antagonists (ondansetron) or 5-HT(4) antagonists (GR 125,487) were infused for 120 min. RESULTS: Luminal administration of 5-HT (10(-6) M) initiated duodenal phase II followed by G-MMC and I-MMC with a concomitant increased release of plasma motilin. The duodenal 5-HT concentration was significantly increased during phase II (59 +/- 9 ng/ml) and phase III (251 +/- 21 ng/ml) compared to that of phase I (29 +/- 5 ng/ml). On the other hand, the 5-HT content in the stomach was not significantly changed throughout the MMC cycle. Intravenous infusion of motilin (0.3 microg/kg/h) increased the luminal 5-HT content and induced G-MMC and I-MMC. 5-HT(4) antagonists significantly inhibited both G-MMC and I-MMC, while 5-HT(3) antagonists inhibited only G-MMC. CONCLUSION: It is suggested that the MMC cycle is mediated by a positive feedback mechanism via the interaction between motilin and 5-HT.
Authors: Per M Hellström; Jan Tack; Lakshmi Vasist Johnson; Kimberley Hacquoil; Matthew E Barton; Duncan B Richards; David H Alpers; Gareth J Sanger; George E Dukes Journal: Br J Pharmacol Date: 2016-04-13 Impact factor: 8.739