Adiponectin ; Ghrelin ; physiology ; Growth Hormone-Releasing Hormone ; Humans ; Leptin ; Receptors, Ghrelin ; Resistin

Ghrelin, a novel gastrointestinal peptide with 28 amino acids, is secreted from the A-like cells of the gastric fundus. This peptide hormone does not only promote the release of growth hormone, but also stimulates food intake, gastric motility and cardiac output. Increased plasma ghrelin level has been reported in patients with upper gastrointestinal (GI) disease or in their disease animal model, suggesting its important role in the pathogenesis of upper GI disease.
Appetite/*physiology ; Cysteamine/metabolism ; Dyspepsia/etiology ; *Eating ; Gastrointestinal Diseases/*etiology ; Ghrelin/*physiology ; Humans ; Peptic Ulcer/etiology

OBJECTIVETo investigate the effect of the expression of ghrelin receptors on the postoperative small intestine dysmotility in rat models.

METHODSThe effect of different concentrations of ghrelin (0, 0.01, 0.1, 0.5, 1.0 μmol/L) on the contraction of smooth muscle strips of rat small intestine in the presence or absence of carbachol was observed in vitro. End-to-side anastomosis was performed in the study group and sham controls were used. The expression of ghrelin receptors(GHS-R1a) in small intestine muscle layers was detected by immunohistochemistry and Western blot.

RESULTSIn vitro, ghrelin enhanced the contraction of smooth muscle strips in the presence of carbachol, and the differences in contraction induced by different concentrations of ghrelin(0.1, 0.5, 1.0 μmol/L) were statistically significant [(223±18)%, (245±22)%, (264±25)%, P<0.01]. Immunohistochemistry study showed that GHS-R1a mainly located in the muscular layer of the bowel wall. The expression of GHS-R1a in the circular and longitudinal muscle was significantly weaker than that in the control group. The expression of ghrelin receptors after surgery was down-regulated in the study group, which was lower than that in the control group(0.51±0.02 vs. 0.71±0.01, P<0.01).

CONCLUSIONDown regulation of ghrelin receptors in small intestine muscle layers may contribute to the occurrence of small intestine dysmotility after intestinal surgery.

Animals ; Down-Regulation ; Gastrointestinal Motility ; drug effects ; physiology ; Ghrelin ; pharmacology ; Intestine, Small ; drug effects ; metabolism ; physiology ; surgery ; Male ; Postoperative Period ; Rats ; Rats, Sprague-Dawley ; Receptors, Ghrelin ; metabolism

OBJECTIVETo study the relationship between Ghrelin and growth hormone secretagogue receptor (GHSR) expression and the catch-up growth in rats with intrauterine growth restriction (IUGR).

METHODSThe rat model of IUGR was established by food restriction during pregnancy. The small for gestational age (SGA) and appropriate for gestational age (AGA) rat pups from the pregnant rats were used as the experimental group. The AGA rat pups from the pregnant rats without food restriction served as the control group. The samples from the stomach fundus and hypothalamus were taken postnatal days 0, 20 and 40. Ghrelin mRNA and GHSR mRNA expression were determined by real-time fluorescence quantitative PCR (real-time FQ-PCR). Ghrelin protein and GHSR protein expression were examined by immunohistochemistry (IHC).

RESULTSAt postnatal day 0, both Gherlin mRNA and protein levels in the stomach fundus were significantly higher, while GHSR mRNA expression in the hypothalamus were significantly lower in SGA rats from food restriction group than those in AGA rats from restriction and control groups. At postnatal day 20, the ghrelin protein expression in the stomach of fundus, and GHSR mRNA and protein expression in the hypothalamus in SGA catch-up rats were significantly higher than those in SGA non-catch-up growth rats and AGA rats from the control group. At postnatal day 40, there were no significant differences among SGA catch-up growth rats, SGA non-catch-up growth rats and normal AGA rats.

CONCLUSIONSGhrelin-GHSR might be involved in the physiological regulation and pathological process in IUGR rats. It is also possibly involved in the regulation of catch-up growth in the early life of SGA rats.

Animals ; Female ; Fetal Growth Retardation ; physiopathology ; Gastric Fundus ; chemistry ; Ghrelin ; analysis ; genetics ; physiology ; Growth ; Hypothalamus ; chemistry ; Immunohistochemistry ; Pregnancy ; Rats ; Receptors, Ghrelin ; analysis ; genetics

The brain-gut peptide ghrelin, a endogenous ligand for the growth hormone secretagogue hormone receptor, is mainly produced by gastric cells in the periphery, regulating energy metabolism via stimulating the appetite. Inside the brain, ghrelin is mainly expressed in the pituitary and in the hypothalamic arcuate nucleus, regulating the synthesis and secretion of neuropeptides that are correlated with feeding behavior, reproduction, and stress responses. Recently, more and more researches focused on the regulating roles of ghrelin on learning and memory, and mood regulation have indicated that ghrelin may inhibit neuronal apoptosis, improve cognitive function, and regulate the activities of neuroendocrine systems such as the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis thus get involved in the pathogenesis of neuropsychiatric diseases. The aim of this review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin in the brain.
Apoptosis ; Brain ; metabolism ; pathology ; physiology ; Ghrelin ; metabolism ; physiology ; Humans ; Learning ; Memory ; Neurons ; pathology ; Parkinson Disease ; metabolism ; pathology ; physiopathology

OBJECTIVETo investigate the effects of Ghrelin on the expression of acyl coenzyme A:cholesterol acyltransferases-1 (ACAT-1) in THP-1 derived foam cells.

METHODSThe human monocytic leukemia cell line (THP-1) was chosen in our study. The differentiation of THP-1 cells into macrophages was induced by phorbol 12-myristate 13-acetate. Macrophages were then incubated with oxidized LDL (ox-LDL) to generate foam cells. Ghrelin and [D-Lys3]-GHRP-6, the special antagonist of growth hormone secretagogue receptor (GHS-R), were treated during foam cells formation. The ACAT-1 protein and mRNA levels were detected by Western blot and RT-PCR. The effect of variance of cholesterol content was measured by zymochemistry via-fluorospectrophotometer.

RESULTSGhrelin reduced the content of cholesterol ester in foam cells obviously. ACAT-1 protein and mRNA levels were also decreased. The antagonist of GHS-R inhibited the effects of Ghrelin on ACAT-1 expression in dose-dependent manner. The ACAT-1 mRNA levels of the GHS-R specific antagonist groups (10(-5), 5 x 10(-5), 10(-4) mol/L) were 1.14 +/- 0.04, 1.58 +/- 0.03, 2.40 +/- 0.16, significantly higher than that of the Ghrelin group (0.89 +/- 0.05). And the protein expressions were 1.25 +/- 0.09, 1.77 +/- 0.11, 2.30 +/- 0.09, also higher than that of the Ghrelin group (0.86 +/- 0.08).

CONCLUSIONSGhrelin might interfere atherosclerosis by down-regulating the expression of ACAT-1 via GHS-R pathway.

Acetyl-CoA C-Acetyltransferase ; metabolism ; Acyl Coenzyme A ; metabolism ; Blotting, Western ; Cell Line, Tumor ; Cholesterol ; metabolism ; Down-Regulation ; Foam Cells ; metabolism ; Ghrelin ; physiology ; Humans ; RNA, Messenger ; metabolism ; Receptors, Ghrelin ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Spectrophotometry

OBJECTIVETo investigate the effect and mechanism of ghrelin and its synthetic peptide GHRP-6 on gastric motor in mice.

METHODSIn vivo, the dose-dependent effects of ghrelin (20,50,100,200 mug/kg) and GHRP-6 (20,50,100,200 mug/kg) on gastric emptying were measured by intragastric application of phenol red test which was adapted for use in mice. The effects of atropine, NG-nitro-L-arginine methyl ester (L-NAME), and D-Lys(3)-GHRP-6 (GHS-R antagonist) on the gastric motor induced by ghrelin and GHRP-6 (100 mug/kg) were also investigated. In vitro, the effects of ghrelin (0.01,0.1,1.0,10.0 mumol/L) and GHRP-6 (0.01,0.1,1.0,10.0 mumol/L) on spontaneous contraction of mice fundic muscle strips were studied as well.

RESULTSBoth ghrelin (50,100,200 mug/kg) and GHRP-6 (50,100,200 mug/kg) significantly accelerated gastric emptying (P<0.05), but they failed to accelerate gastric emptying in the presence of atropine, L-NAME and D-Lys(3)-GHRP-6 (P<0.05). Ghrelin (0.1, 1.0, 10.0 mumol/L) and GHRP-6 (0.1, 1.0, 10.0 mumol/L) induced significant contraction of fundic muscle strips in concentration-dependent manner (P<0.05), which could be blocked by tetrodotoxin.

CONCLUSIONGhrelin and its synthetic peptide GHRP-6 accelerate gastric emptying perhaps by activating GHS-R of cholinergic excitatory pathways and nitrergic nervous pathways in the enteric nervous system.

Animals ; Female ; Gastric Emptying ; drug effects ; Ghrelin ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Stomach ; drug effects ; physiology

OBJECTIVETo investigate the effect of growth hormone secretagogue(ghrelin) on the contraction and relaxation of small intestinal smooth muscle in rats and its mechanism.

METHODSTwenty-four vagotomized rats were injected intraperitoneally with different concentrations of ghrelin (0, 20, 40, 80 μg/kg). The small intestinal transit were observed. The effect of ghrelin(0.01, 0.1, 0.5, 1.0 μmol/L) on the contraction and relaxation of rat small intestinal smooth muscle strips was observed in vitro in the presence of carbachol(50 nmol/L), the locations of ghrelin receptors(GHS-R1a) on different cells in small intestinal muscle layers were detected by immunofluorescence.

RESULTSWith the increase of concentrations, ghrelin elevated the percentage of small intestinal transit[(25.4±1.0)%, (33.7±1.9)%, (39.3±2.4)%, (44.7±2.1)%] in a dose-dependent manner, and the differences were statistically significant among groups(P<0.05). Ghrelin could also enhance the contraction [(67.0±2.4)%,(149.5±3.3)%, (187.1±4.7)%, (213.5±3.4)%] and relaxation[(35.3±1.1)%, (62.9±3.8)%, (79.6±2.7)%, (94.6±2.2)%] of smooth muscle strips mediated by Cch in a dose-dependent manner, and the differences were statistically significant among groups(P<0.05). Immunofluorescence revealed that ghrelin receptors mainly located on membrane of the nerve cells in the muscle layers, while no receptors were observed on membrane of the smooth muscle cells.

CONCLUSIONGhrelin may enhance the effect of the contraction and relaxation of the rat small intestinal smooth muscle mediated by cholinergic neurotransmitters by activating the nerve cells in the enteric plexus.

Animals ; Gastrointestinal Motility ; Ghrelin ; pharmacology ; Intestine, Small ; drug effects ; physiology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle, Smooth ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the effect of ghrelin on the duodenal myoelectrical activity during the feeding state and the fasting state in rats. METHODS: One pair of bipolar silver electrodes were chronically implanted in the duodenal serosa of rats for electromyography. The myoelectrical activity was recorded when ghrelin was injected intravenously into rats during the feeding state or the fasting state. Some rats were pretreated with atropine, phentolamine, propranolol, L-arginine, and (D-Lys3)GHRP-6 respectively to explore the mechanism of ghrelin. RESULTS: Duodenal migrating myoelectrical complex (MMC) could be induced by ghrelin in the feeding state. Ghrelin could shorten the length of duodenal MMC cycle and increase the amplitude and frequency of phase III during the fasting state. The percentage of phase III in the MMC cycle did not change. These effects were inhibited by atropine and L-arginine (D-Lys3)GHRP-6, but not by propranolol and phentolamine. CONCLUSION Ghrelin seems to be closely related to the duodenal motility. The excitatory effect of ghrelin on duodenal MMC might rely on the cholinergic pathway, and have a close relationship with NO. The receptor of ghrelin can regulate its activity.
Animals ; Duodenum ; drug effects ; physiology ; Electromyography ; Female ; Gastrointestinal Motility ; drug effects ; Ghrelin ; pharmacology ; Male ; Muscle, Smooth ; physiology ; Myoelectric Complex, Migrating ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of ghrelin on small intestinal transit and intergigestive gastrointestinal migrating myoelectric complex (MMC) in rats.

METHODSAfter a 24-hour fasting, the rats with or without pretreatment with receptor antagonist (D-Lys3)GHRP-6 were given intravenous injections of ghrelin at different doses to observe the changes in small intestinal transit. The MMCs of the fasting rats were recorded using a multilead physiological recording system, and their changes observed in response to intravenous ghrelin injections, or to ghrelin injection following pretreatment with atropine, phentolamine, propranolol, L-arginine or (D-Lys3)GHRP-6, respectively.

RESULTSGhrelin enhanced the small intestinal transit dose-dependently, and this effect was inhibited by application of ghrelin receptor antagonist. Ghrelin also showed excitatory effect on the MMCs, which was inhibited by atropine, L-arginine or (D-Lys3)GHRP-6, but not by propranolol and phentolamine.

CONCLUSIONGhrelin can promote gastrointestinal motilities, and its excitatory effects rely on the cholinergic pathway in close relation to nitric oxide pathway. Ghrelin receptor is involved in its action in promoting the gastrointestinal motilities.

Animals ; Dose-Response Relationship, Drug ; Female ; Gastrointestinal Motility ; drug effects ; physiology ; Gastrointestinal Transit ; drug effects ; physiology ; Ghrelin ; administration & dosage ; pharmacology ; Injections, Intravenous ; Intestine, Small ; drug effects ; physiology ; Male ; Myoelectric Complex, Migrating ; drug effects ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley