Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats

Abstract

Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.

Endogenous orexin-A in the brain mediates 2-deoxy-d-glucose-induced stimulation of gastric motility in freely moving conscious rats

“…Functional gastrointestinal disorders (FGIDs) are characterized as 16 chronic or recurrent GI symptoms, which are not explained by structural or biochemical abnormalities. Brain-gut interaction plays an important role in the pathophysiology of FGIDs [44].…”

“…Gastric motility was measured by manometric methods described in previous study [16]. Conscious animals without fasting were put in wire-bottom and non-restraint polycarbonate cages.…”

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

“…This seems to be an indirect effect mediated via the hypothalamus by the activation of anorexigenic cocaine-and amphetamineregulated transcripts as well as urocortin gene expression (Asakawa et al 2005). Similarly, obestatin has also been described as an inhibitor of motor activity in the gastroduodenal region in the fed state, but not in the fasted state, an effect that seems to be an indirect action in which CRH type 1 and type 2 receptors might be involved (Ataka et al 2008). However, obestatin was unable to antagonize AG-induced stimulation of gastroduodenal motility (Ataka et al 2008).…”

“…Similarly, obestatin has also been described as an inhibitor of motor activity in the gastroduodenal region in the fed state, but not in the fasted state, an effect that seems to be an indirect action in which CRH type 1 and type 2 receptors might be involved (Ataka et al 2008). However, obestatin was unable to antagonize AG-induced stimulation of gastroduodenal motility (Ataka et al 2008).…”

The role of ghrelin in energy homeostasis and its potential clinical relevance (Review)

“…Peripheral obestatin inhibits gastric emptying. Obestatin has clearly been shown to act via the corticotropinreleasing factor (CRF) receptor subtypes 1 and 2 in the brain to inhibit motor activity in the antrum and duodenum in conscious fed rats (57). However, other studies have shown that obestatin does not affect gastric and intestinal motility in vivo or in vitro (58)(59)(60).…”