Effects of ghrelin on interdigestive contractions of the rat gastrointestinal tract

Abstract

In the interdigestive state, the stomach and small intestine show a remarkable motor pattern, known as the migrating motor complex (MMC) [1] . MMC consists of three phases; phaseⅠ(period of motor quiescence), phase Ⅱ (period of irregular low amplitude contractions) and phase Ⅲ (period of regular high amplitude contractions). In humans and dogs, MMC is usually observed every 90-120 min in the interdigestive state. In contrast, in rats, MMC cycle is less than 20 min and not so regular, compared to humans and dogs [2,3] . Exogenously administered motilin does not induce phase Ⅲ-like contractions in rats. Motilin or its receptors are not found in rats [4] . Ghrelin, a 28-amino acid peptide, was discovered as the endogenous ligand for growth hormone secretagogue receptor (GHS-R) from the rat stomach [5] . Because of a structural resemblance to motilin, ghrelin is known as the motilin-related peptide [6,7] . Ghrelin administration causes phase Ⅲ-like contraction at the antrum and duodenum in conscious rats [3,8] . We recently showed that gastric spontaneous phase Ⅲ-like contractions were abolished by ghrelin receptor antagonists [9] . This suggests that endogenous ghrelin regulates spontaneous phase Ⅲ-like contractions of the rat stomach.However, it still remains unknown whether ghrelin regulates intestinal phase Ⅲ-like contractions in rats. In the current study, we investigated whether exogenously administered ghrelin stimulates phase Ⅲ-like contractions of gastrointestinal (GI) tract in conscious rats. EFFECTS OF GHRELIN ON THE INTERDIGESTIVE GI CONTRACTIONSMale Sprague-Dawley rats weighing 280-340 g were kept AbstractGhrelin causes interdigestive contractions of the stomach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted on the antrum, duodenum, proximal and distal jejunum. After an overnight fast, gastrointestinal (GI) contractions were recorded in freely moving conscious rats. Spontaneous phase Ⅲ-like contractions were observed at every 13-16 min in rat GI tract. The fasted motor patterns were replaced by the fed motor pattern immediately after food intake. Two minutes after finishing the spontaneous phase Ⅲ-like contractions in the antrum, acyl ghrelin (0.8, 2.4 and 8.0 µg/kg per min) was continuously infused for 30 min. Three-five minutes after the starting ghrelin infusion, augmented phase Ⅲ-like contractions were observed at the antrum, duodenum, and jejunum. Ghrelin infusion (0.8, 2.4 and 8.0 µg/kg per min) significantly increased motility index of phase Ⅲ-like contractions at the antrum and jejunum in a dose dependent manner, compared to that of saline injection. Thus, it is likely that exogenously administered ghrelin causes phase Ⅲ-like contraction at the antrum, which migrates to the duodenum and jejunum. The possible role of 5-HT, in addition to ghrelin, in mediating intestinal migrating motor complex (MMC), is discussed.

Vagal Nerve Regulation Is Essential for the Increase in Gastric Motility in Response to Mild Exercise

“…It remains to be determined whether lower blood glucose resulting from mild exercise has a similar effect. Ghrelin has been demonstrated to regulate interdigestive contractions in rats (Taniguchi et al 2008). Such effect of ghrelin can be blocked by vagotomy in vivo.…”

Down-regulation of ghrelin receptors in the small intestine delays small intestinal transit in vagotomized rats

“…When the vagal nerve was cut, these effects were abolished (18). Peripheral administration of ghrelin also enhanced motility of the gastrointestinal tract (14,15,17,37 ]-GHRP-6 blocked the effect of ghrelin. These results suggest that ghrelin affects small intestinal motility by activating ghrelin receptors (GHS-R1a).…”

“…This may be the main factor leading to delayed small intestinal transit. Ghrelin can promote gastrointestinal tract motility if administered through central or peripheral channels (13,(15)(16)(17). Ghrelin exerts its role by activating ghrelin receptors (GHS-R1a) in central or peripheral tissues (2)(3)(4)(5).…”

“…Following this discovery, a wide variety of biological functions of ghrelin have been determined. It is known to stimulate appetite (10) and a positive energy balance (11); it has cardiovascular actions (12) and controls digestive motility (13)(14)(15).…”

The Gut Peptide Hormone Family, Motilin and Ghrelin

“…Since the ghrelin receptor is expressed in the gastrointestinal tract, the effect of ghrelin on gastric motility has also been examined. In rats, ghrelin exerts stimulatory effects on motility of the antrum and duodenum in both fed and fasted states (Fujimiya, et al 2008), and Taniguchi et al reported that ghrelin infusion significantly increased motility index of phase III-like contractions at the antrum and jejunum in a dose dependent manner (Taniguchi, et al 2008). As well as the rat stomach, phase III-like contractions in mice were observed in the interdigestive state, and no spontaneous phase III-like contractions were found in vagotomized mice, suggesting that ghrelin-induced gastric phase III-like contractions are mediated via vagal cholinergic pathways in mice (Zheng, et al 2009).…”