Intermittent Esophageal Hypotensive Peristalsis Re-Assessed With Multiple Rapid Swallowing

Abstract

We recently proposed the usefulness of the house musk shrew (Suncus murinus ) as a model animal for motilin study because this animal produces a motilin family peptide and shows the phasic interdigestive gastric contraction. This gastric motor contraction includes phase I, phase II and phase III contractions as found in dogs and humans. In the DDW 2010, we reported that cumulative ghrelin administration and pretreatment with a low dose of motilin (10−10 M) synergistically induced gastric contraction in a dose-dependent manner, suggesting that ghrelin is involved in the migrating motor complex (MMC) and has a complementary effect with motilin. To clarify the effects of these family peptides on each phase in the MMC, we administrated an antagonist of motilin or ghrelin into a force transducer-sutured freemoving suncus. At 10-20 min after the beginning of phase II contraction, MA-2029 (1 mg kg−1 h−1, motilin receptor antagonist) or saline was continuously infused for 2 h, and we found that phase II-like contraction was prolonged and that no phase III contraction occurred during the infusion of MA-2029. The duration from the start of infusion of the motilin antagonist and phase III contraction was significantly longer (182 ± 12 min) than that in controls (71 ± 6 min, P<0.05). These results indicate that motilin has no effect on continuing phase II contraction but is essential for induction of phase III contraction. The frequencies of phasic contraction with saline treatment and MA-2029 treatment were almost the same in phase II (saline: 14 ± 0.7 min−1, MA-2029: 13 ± 0.7 min−1). Although bolus administration of motilin (300 ng kg−1 i.v.) significantly induced phase III-like contraction in the control suncus In Vivo, during the infusion of MA-2029, motilin administration (300 ng kg−1) did not evoke phase III-like contraction. On the other hand, continuous infusion of D-Lys3GRHP6 (6 mg kg−1 h−1, ghrelin receptor antagonist) for 2 h inhibited phase II contraction and completely suppressed phase III contraction, and phase II contraction restarted after the end of infusion. The results of this study together with the results of our previous study showing that ghrelin administration (0.1, 0.2 μg kg−1 min−1 for 10 min i.v.) in phase II of MMC significantly enhanced gastric contraction in a dose-dependent manner indicated that MMC in the free-moving suncus stomach is coordinated by endogenous motilin and ghrelin. Phase II contraction may be initiated by endogenous ghrelin, and subsequent increase in motilin induces following phase III contraction.