Function of ghrelin and ghrelin receptors in the network regulation of gastric motility

Abstract

Numerous previous studies have demonstrated that ghrelin promotes gastric motility when administered peripherally. This effect appears to be regulatory but not directly stimulatory, and therefore may involve a number of complex mechanisms. In the periphery, ghrelin may affect gastric motility through intercellular networks among interstitial cells of Cajal, myenteric nerve cells and smooth muscle cells. The aim of the present study was to investigate the effects and possible mechanisms underlying this hypothesis. The effects of ghrelin on the contraction force of gastric antrum smooth muscle strips of rats were studied in the presence or absence of carbachol (CCh), [D‑Lys3]‑GHRP‑6, atropine, tetrodotoxin (TTX) and nimodipine in vitro. The expression of ghrelin receptors (GHS‑Rs) on different cell types in gastric muscle layers was observed by means of immunofluorescence. Ghrelin enhanced smooth muscle strip contraction induced by CCh, but when CCh was absent, this effect was eliminated. Atropine and nimodipine eradicated the muscle strip contraction enhanced by ghrelin, while [D‑Lys3]‑GHRP‑6 was only able to partly block this effect and TTX had no effect on muscle strip contraction. It was identified that ghrelin had no effect on the contractive rhythm of the strips. GHS‑R1s were located differentially depending on the cell type, including myenteric nerve cells, interstitial cells of Cajal and smooth muscle cells. In conclusion the present study demonstrated that ghrelin may act as an adjuvant to regulate gastric smooth muscle contraction induced by CCh through GHS‑R1s, which are expressed on myenteric nerve cells, Cajal cells and smooth muscle cells. Ghrelin may exert its effects by influencing the functional status of different cell types in the gastric muscle layer to subsequently enhance the contractive effect of cholinergic neurotransmitters and enhance gastric motility.

Ghrelin and gastrointestinal stromal tumors

“…Ghrelin receptors are expressed in several types of tumors, including gastric and colon cancer, and are able to promote tumor growth[9-11]. The Cajal cells from which GISTs arise both produce ghrelin and express the ghrelin receptor[12]. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown.…”

Ghrelin Stimulates Hepatocyte Proliferation via Regulating Cell Cycle Through GSK3β/Β-Catenin Signaling Pathway

“…Consistently, high level of GHS-R1a is expressed in hypothalamic nuclei, pituitary gland and the spinal cord [21]. Emerging evidences also indicate the presence of GHS-R1a in the peripheral tissues such as enteric nervous system [22], pancreatic islets [23], adipose tissue [24] and skeletal muscle [25]. The expression of GHS-R1a in peripheral tissues indicates a direct peripheral mechanism for the physiological functions of circulating ghrelin.…”

Distribution of ghrelin-positive mast cells in rat stomach

“…Thus, sympathetic nerves stimulate directly ghrelin secretion [69][70][71][72]. According to Yang et al [73], ghrelin may regulate gastric smooth muscle contraction induced by cholinergic neurotransmitters using GHS-R1s, which are expressed on myenteric nerve cells, interstitial cells of Cajal and smooth muscle cells. The mentioned features of ghrelin could be used for explanation of the observed Ghr + MC localization in the muscular layers of rat stomach.…”