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复习生长激素促分泌素受体(GHS R)及其内源性配体ghrelin的获得和特点,综合分析两者对胃肠动力方面的影响和机制,以及它们在治疗胃肠动力障碍的前景。 相似文献
4.
Sánchez J Oliver P Picó C Palou A 《Pflügers Archiv : European journal of physiology》2004,448(5):500-506
We investigated diurnal changes in leptin and ghrelin levels in the stomach and in the systemic circulation and their relation to food intake rhythms in Wistar rats housed at 22 °C with a 12-h light/dark cycle and free access to food and water. Animals were sacrificed every 3 h over a 24-h period. Leptin and ghrelin levels in serum and in the gastric mucosa were analysed by immunoassay. Leptin mRNA levels were determined in the gastric mucosa by RT-PCR and in different adipose tissue depots (epididymal, retroperitoneal and mesenteric) by Northern blot. Ghrelin mRNA levels were determined by Northern blot. Gastric and serum leptin levels displayed similar diurnal rhythms, rising during the dark phase and decreasing gradually during the light phase. Leptin expression in the different adipose tissue depots correlated positively with circulating leptin levels (P<0.05), although there were some depot-associated differences. Leptin mRNA levels in the mesenteric depot correlated positively with food intake (P<0.05). In blood, ghrelin levels rose sharply just before the onset of the dark phase and dropped suddenly just after. In the stomach, ghrelin levels were high during the fasting period of light and low during the night, and correlated inversely with food intake, gastric contents and serum leptin levels (P<0.05). Leptin and ghrelin in the stomach and in the systemic circulation thus show diurnal variations that are influenced by food intake rhythms. The results agree with a role for ghrelin as a stimulant of meal initiation. 相似文献
5.
Ghrelin expression in hyperplastic and neoplastic proliferations of the enterochromaffin-like (ECL) cells 总被引:1,自引:0,他引:1
Ghrelin, a recently discovered peptide isolated from the gastric corpus mucosa, is believed to be important in the regulation
of growth hormone secretion and has been shown to increase appetite and food intake as well. It may also have other gastrointestinal
and cardiac functions. Because a cell of origin for ghrelin has not been convincingly identified in the gastric mucosa thus
far, we studied the immunohistochemical expression of ghrelin in proliferative lesions of the enterochromaffin-like (ECL)
cells—a cell that is not only exclusively confined to the gastric corpus mucosa but is its dominant endocrine cell type as
well.
Formalin-fixed, paraffin embedded tissues from three cases of gastric ECL cell hyperplasia and five ECL carcinoids (three
with coexisting foci of diffuse, linear, and micronodular hyperplasia) were immunohistochemically stained for ghrelin, using
a commercially available antibody. The Sevier-Munger stain for ECL cells and immunohistochemical stains for chromogranin,
gastrin, serotonin, somatostatin, and vesicular monoamine transporter-2 (VMAT-2) were performed on parallel sections for correlation
with the ghrelin staining results.
All ECL cell carcinoids and hyperplastic lesions were positive for both the Sevier-Munger and the immunohistochemical stains
for chromogranin and VMAT-2. Immunoreactivity for ghrelin was seen in 4/5 ECL carcinoids, all cases of ECL cell hyperplasia,
as well as in all areas with linear and micronodular hyperplasia adjacent to the ECL cell carcinoids. In each instance, such
staining was confined to the Sevier-Munger, and VMAT-2 positive cells only.
Our findings indicate that the ECL cells are either the ghrelin-producing cells of the gastric mucosa or acquire the capability
to synthesize ghrelin during proliferative states encompassing the entire hyperplasia to neoplasia spectrum. In view of the
orexigenic and other known actions of ghrelin, the functional and/or biologic significance of ghrelin production in such ECL
cell proliferations needs to be investigated further. 相似文献
6.
Binge eating disorder (BED), characterized by ingestion of very large meals without purging afterwards, is found in a subset of obese individuals. We showed previously that stomach capacity is greater in obese than in lean subjects, and in this study, we investigated capacity in obese individuals with BED. We also determined ad-libitum intake of a test meal until extremely full. Furthermore, we measured various appetitive hormones (insulin, leptin, glucagon, CCK, ghrelin) and glucose before a fixed meal and for 120 min afterwards. An acetaminophen tracer was used to assess gastric emptying rate. We compared three groups of overweight women: 11 BED, 13 BE (subthreshold BED), and 13 non-binge-eating normals. The BED individuals had the largest stomach capacity as assessed by either maximum volume tolerated (P=.05) or by gastric compliance to pressure (P=.02) using an intragastric balloon. Although test meal intake did not differ between groups, it correlated (P=.03) with gastric capacity. The BED group showed a tendency (P=.06) to have greater area under the curve (AUC) and had higher values at 5 and 60 min (P<.05) for insulin compared to normals. Moreover, the BED subjects had lower ghrelin baselines premeal, and lower AUC for ghrelin, which then declined less postmeal than for the normals (P<.05). None of the other blood values differed, including glucose, leptin glucagon, and CCK, as well as acetaminophen, reflecting gastric emptying. The lower ghrelin in BED, although contrary to what was expected, is consistent with lower ghrelin in obesity, and suggests down-regulation of ghrelin by overeating. The lack of differences in CCK is consistent with the lack of differences in gastric emptying rate, given that CCK is released when nutrients reach the intestine. The results show that BED subjects have a large gastric capacity as well as abnormalities in meal-related ghrelin and insulin patterns that may be factors in binge eating. 相似文献
7.
The presence and distribution patterns of ghrelin, a gastric acylated peptide, were studied in the entire gastrointestinal tract of the chicken (Gallus domesticus) using the peroxidase-antiperoxidase immunohistochemical method, western blot analysis and a specific antibody against the C-terminal region of rat ghrelin. Ghrelin-immunopositive cells were observed in the mucosal layer of all segments examined. The largest numbers of ghrelin-positive cells were located at the base of lobuli of the proventriculus gland, along villi of the intestines and in crypts of the duodenum. Lower numbers of ghrelin-immunostained cells were located in crypts of jejunum and ileum and only few ghrelin-immunostained cells were detected at the base of crypts of the large intestine. Closed and open types of cells were observed in all segments. Western blot analysis confirmed the presence of ghrelin-like protein in the entire chicken gastrointestinal tract. The anatomical distribution patterns and the morphological characteristics of chicken ghrelin-positive cells suggest that they are endocrine cells. Furthermore, it is concluded that ghrelin shows a high degree of preservation during evolution from non-mammalian vertebrates to mammals. 相似文献
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Neuropeptides play an important role in modulating seizures and epilepsy. Unlike neurotransmitters which operate on a millisecond time-scale, neuropeptides have longer half lives; this leads to modulation of neuronal and network activity over prolonged periods, so contributing to setting the seizure threshold. Most neuropeptides are stored in large dense vesicles and co-localize with inhibitory interneurons. They are released upon high frequency stimulation making them attractive targets for modulation of seizures, during which high frequency discharges occur. Numerous neuropeptides have been implicated in epilepsy; one, ACTH, is already used in clinical practice to suppress seizures. Here, we concentrate on neuropeptides that have a direct effect on seizures, and for which therapeutic interventions are being developed. We have thus reviewed the abundant reports that support a role for neuropeptide Y (NPY), galanin, ghrelin, somatostatin and dynorphin in suppressing seizures and epileptogenesis, and for tachykinins having pro-epileptic effects. Most in vitro and in vivo studies are performed in hippocampal tissue in which receptor expression is usually high, making translation to other brain areas less clear. We highlight recent therapeutic strategies to treat epilepsy with neuropeptides, which are based on viral vector technology, and outline how such interventions need to be refined in order to address human disease. 相似文献
10.
Raff H 《Endocrine》2003,21(2):159-161
Hypoxia is well known to decrease appetite and weight gain in growing rats, and to induce weight loss in humans. It has been
hypothesized that this is mediated by a change in ghrelin, an orexigenic peptide synthesized and released primarily from the
stomach. Rats were exposed to hypoxia for 7 d as neonates (birth-7 d of age), weanlings (28–35 d of age), and juveniles (49–56
d of age). Hypoxia had no effect on total or active plasma ghrelin. There was a significant decrease in active ghrelin in
weaned rats (0.8±0.1 ng/mL) compared to nursing pups at 7 d of age (2.3±0.2 ng/mL). The proportion of total ghrelin that was
active decreased significantly between 7 and 35 d of age. We conclude that the anorexia and weight loss associated with hypoxia
is probably not mediated by ghrelin. There appear to be changes in active ghrelin levels in plasma during early development
in the rat. 相似文献