Ghrelin and Motilin Control Systems in GI Physiology and Therapeutics

Abstract

Ghrelin and motilin are released from gastrointestinal endocrine cells during hunger, to act through G protein-coupled receptors that have closely related amino acid sequences. The actions of ghrelin are more complex than motilin because ghrelin also exists outside the GI tract, it is processed to des-acyl ghrelin which has activity, ghrelin can exist in truncated forms and retain activity, the ghrelin receptor can have constitutive activity and is subject to biased agonism and finally additional ghrelin-like and des-acyl ghrelin receptors are proposed. Both ghrelin and motilin can stimulate gastric emptying, acting via different pathways, perhaps influenced by biased agonism at the receptors, but research is revealing additional pathways of activity. For example, it is becoming apparent that reduction of nausea may be a key therapeutic target for ghrelin receptor agonists and perhaps for compounds that modulate the constitutive activity of the ghrelin receptor. Reduction of nausea may be the mechanism through which gastroparesis symptoms are reduced. Intriguingly, a potential ability of motilin to influence nausea is also becoming apparent. Ghrelin interacts with digestive function through its effects on appetite, and ghrelin antagonists may have a place in treating Prader-Willi syndrome. Unlike motilin, ghrelin receptor agonists also have the potential to treat constipation by acting at the lumbosacral defecation centres. In conclusion, agonists of both ghrelin and motilin receptors hold potential as treatments for specific subsets of digestive system disorders.

Comparison of the effect by which gastric plication and sleeve gastrectomy procedures alter metabolic and physical parameters in an obese type 2 diabetes rodent model

“…hormone metabolism [24]. Studies also report that ghrelin is associated with food intake, energy metabolism, neurotrophy, memory, sleep, and gastric function [25][26][27]. We found that ghrelin was decreased in the GP and SG groups (Fig.…”

Advances in the physiology of gastric emptying

“…Ghrelinand motilin act to accelerate gastric emptying and are released in the inter‐digestive (fasting) period . No gastric accelerating hormones are released in the digestive period.…”

“…Ghrelinand motilin act to accelerate gastric emptying and are released in the inter-digestive (fasting) period. 105 No gastric accelerating hormones are released in the digestive period. Ghrelin is released from G cells in the stomach and the ghrelin-containing neurons in the hypothalamus.…”

Contribution of ghrelin to functional gastrointestinal disorders’ pathogenesis

“…Its mRNA is also found in small and large intestine cells, in pancreatic alpha and beta islet cells, in kidney glomeruli and, to a certain degree, in most human tissues[14,19,21-23]. In secretory granules of endocrine cells in the upper small intestine, ghrelin is colocalized with motilin, a peptide hormone involved in phase III of the migrating motor complex[24,25].…”

“…The receptor’s gene is located on the large arm of chromosome 3, and its mRNA product can be alternatively spliced to two different transcripts, 1a and 1b; however, it is only the 1a mRNA protein product, GHSR1a, which can bind ghrelin[26]. GHSR1a also displays constitutive activity[24]. Type 1a mRNA has been found in the arcuate and ventromedial nuclei of the hypothalamus, in the pituitary, thyroid gland, and adrenals, whereas the type 1b mRNA is ubiquitously present in human tissue[19,22].…”