Growth hormone secretagogue participates in two-way regulation of the motility of small intestinal smooth muscle in rats / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of growth hormone secretagogue(ghrelin) on the contraction and relaxation of small intestinal smooth muscle in rats and its mechanism.</p><p><b>METHODS</b>Twenty-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.</p><p><b>RESULTS</b>With 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.</p><p><b>CONCLUSION</b>Ghrelin 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.</p>

Effect and mechanism of ghrelin and its synthetic peptide growth hormone releasing peptide 6 on gastric motor in mice / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of ghrelin and its synthetic peptide GHRP-6 on gastric motor in mice.</p><p><b>METHODS</b>In 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.</p><p><b>RESULTS</b>Both 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.</p><p><b>CONCLUSION</b>Ghrelin 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.</p>

Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 (GHRP-6), increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.</p><p><b>METHODS</b>A diabetic guinea pig model was produced by intraperitoneal (i.p.) injection of streptozotocin (STZ, 280 mg/kg). Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 (10 - 100 microg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor (GHS-R) antagonist, D-Lys(3)-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 (100 microg/kg) was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 (0.01 - 10 micromol/L) on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>We established a guinea pig model of delayed gastric emptying. Ghrelin (20, 50, or 100 microg/kg) and GHRP-6 (20, 50, or 100 microg/kg) accelerated gastric emptying in diabetic guinea pigs with gastroparesis (n = 6, P < 0.05). In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 (100 microg/kg) failed to accelerate gastric emptying (n = 6, P < 0.05). D-Lys(3)-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist (n = 6, P < 0.05). Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs (n = 6, P < 0.05). RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.</p><p><b>CONCLUSIONS</b>Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.</p>