Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotensin (NT) is a 13 amino acid peptide found predominantly in the ileum and it is released into the circulation by a meal. Much of the circulating NT consists of N terminal fragments which have no known biological activity. However, the sites and rates of NT metabolism are not known. In the present study the MCR and half-disappearance time of NT were estimated by infusing NT(1-13) into 10 normal subjects. The role of the kidney was assessed by studies in patients with chronic renal failure (CRF). The nature of the metabolites was characterized using region specific antisera and high pressure liquid chromatography (HPLC). The plasma pancreatic polypeptide response to the NT infusion was also measured. The NT MCR in normal subjects was 88 +/- 25 (SEM) ml/min X kg measured with the C terminal antiserum but only 9.9 +/- 0.8 ml/min X kg measured with the N terminal antiserum, a result consistent with the presence of long lasting N terminal fragments. HPLC of the plasma at equilibrium established that only 20% of the immunoreactivity was present as NT(1-13), with the majority as NT(1-8). No C terminal fragment were detected. Similarly, incubation of NT(1-13), 1-8, and 8-13 in plasma in vitro showed that N terminal fragments were stable in plasma, whereas C terminal fragments were completely metabolized. In patients with CRF, basal plasma NT (measured with the C terminal antisera) was significantly elevated and C terminal MCR was reduced by 82% and N terminal MCR by 32%. Thus the major effect of CRF was on the initial degradation of NT(1-13) to N terminal fragments. HPLC showed that over 60% of the NT was present as NT(1-13). In vitro degradation of NT was also slowed in CRF plasma. The increased proportion of intact biologically active NT in the circulation of the CRF patients could also explain the greater increase in pancreatic polypeptide levels during the NT(1-13) infusion. These studies have established that the metabolism of NT is influenced by the kidney and that the presence of predominantly N terminal fragments of NT in the peripheral circulation of normal subjects can be explained by a combination of renal and extrarenal factors.
 ...
PMID:Metabolism of neurotensin and pancreatic polypeptide in man: role of the kidney and plasma factors. 670 91

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.
 ...
PMID:Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men. 673 5

Pancreatic polypeptide was infused intravenously in healthy fasting subjects at 1 pmol kg-1 (n = 7) and 4 pmol kg-1 min-1 (n = 10) producing plasma PP concentrations of 223 +/- 37 pmol/l (mean +/- SEM) and 891 +/- 64 pmol/l respectively. These levels are similar to and four-fold higher than those seen after a normal mixed breakfast in healthy young adults. In a separate study five healthy subjects ingested a small breakfast during infusion of PP on different days at 1 pmol kg-1 min-1 and 2 pmol kg-1 min-1 respectively. PP at 1 pmol kg-1 min-1 caused a marked reduction in fasting plasma motilin concentrations to 20% of the basal level (p less than 0.001). There were, however, no significant changes in plasma concentrations of insulin, glucagon, gastrin, secretin, enteroglucagon, gastric inhibitory peptide or neurotensin. Despite previous reports possibly implicating PP in metabolism, there were no significant effects on blood levels of glucose, alanine lactate, 3-hydroxybutyrate, glycerol or non-esterified fatty acids, either in the fasting state or after the ingestion of food. Although it seems unlikely that PP is a major hormonal regulator of intermediary metabolism in man, its ability to suppress motilin at physiological concentrations suggests the possibility of an indirect influence on digestive motor function.
 ...
PMID:Effects of pancreatic polypeptide on motilin and circulating metabolites in man. 678 20

RIA of cat adrenal tissue extracts revealed a neurotensin-like immunoreactive material concentrated within the medulla of the gland (mean +/- SEM neurotensin concentration, 15.2 +/- 3.6 pmol/g whole gland; 47.9 +/- 18.4 pmol/g microdissected medulla). This immunoreactive material was found to elute in the region of synthetic neurotensin, thus indicating a similarity to the tridecapeptide originally isolated from bovine hypothalamus. Using immunocytochemical procedures at both light and ultrastructural levels, a neurotensin-like immunoreactive material was localized to a subpopulation of noradrenaline-containing cells quite distinct from the previously described enkephalin-immunoreactive chromaffin cells. Correlative ultrastructural observations have identified three morphologically distinct types of chromaffin cells in the medulla, indicating a marked heterogeneity within the noradrenaline cell population. The finding of neurotensin-like immunoreactivity in noradrenaline-containing cells of the cat adrenal medulla provides further evidence in support of the postulated existence of heterogeneous subpopulations of noradrenaline-containing cells and suggests a possible functional interrelationship between neurotensin and catecholamine.
 ...
PMID:Neurotensin-like immunoreactivity in a subpopulation of noradrenaline-containing cells of the cat adrenal gland. 684 18

Synthetic neurotensin was infused into five healthy subjects at a mean dose of 2.3 pmol/kg . min for 30 min, producing a rise in plasma neurotensin concentrations, measured by RIA of 104 +/- 10 (mean +/- SEM) pmol/liter. The mean disappearance half-time on stopping the infusion was 3.8 +/- 0.2 min. The MCR was 16 +/- 1 ml/kg . min, and the apparent space of distribution was 88 +/- 6 ml/kg. During the neurotensin infusions, plasma pancreatic polypeptide rose by 145 +/- 54 pmol/liter. In contrast to results in experimental animals, there was no significant change in the pulse or blood pressure of the subjects or any significant change in blood glucose or plasma concentrations of insulin, glucagon, gastric inhibitory peptide, gastrin, motilin, or vasoactive intestinal peptide. Similarly, there was no change in plasma concentrations of TSH, GH, PRL, LH, and FSH.
 ...
PMID:Neurotensin infusion in man: pharmacokinetics and effect on gastrointestinal and pituitary hormones. 700 47

1. The pathophysiology of the dumping syndrome is poorly understood. Plasma levels of four small intestinal hormones have been measured after an oral glucose provocation test in 19 patients with dumping symptoms and in matched controls. 2. Plasma levels of neurotensin, a newly discovered highly potent, hypotensive ileal peptide, were significantly increased in symptomatic patients compared with those of controls [20 min rise of 43 +/- 6.0 (mean +/- SEM) pmol/l in 19 symptomatic patients, 8.0 +/- 5.5 pmol/l in 20 postoperative symptom-free patients, and 4.1 +/- 3.5 pmol/l in 20 pre-operative patients with duodenal ulcer, P < 0.01]. 3. The rise in enteroglucagon was greater than normal but of similar magnitude to that seen in several other gastrointestinal conditions not associated with dumping symptoms. 4. The release of both gastric inhibitory peptide and motilin did not differ significantly from that of controls.
 ...
PMID:Elevation of plasma neurotensin in the dumping syndrome. 742 91

This study was aimed to investigate, in humans, the possible relationship between plasma neurotensin (NT) levels and the activity of the hypothalamo-pituitary-thyroid axis. Neurotensin was measured by radioimmunoassay in 14 healthy adult volunteers and in 41 patients among whom 10 were considered as controls and 31 had thyroid dysfunction according to free thyroxine and thyrotropin plasma values. Basal NT levels were not significantly different in healthy adults and in control patients: 9.7 +/- 1.1 fmol/ml (mean +/- SEM) vs 13.3 +/- 2.9 fmol/ml, respectively. In patients with central hypothyroidism the NT level was significantly lower (5.7 +/- 1.2 vs healthy volunteers and controls; p < 0.05) and in patients with peripheral hypothyroidism and hyperthyroidism the NT level was significantly higher (35.9 +/- 12.8 and 29.9 +/- 9.5 fmol/ml, respectively, vs healthy adults (p < 0.01) and vs controls (p < 0.05)). After thyrotropin-releasing hormone (TRH) injection (250 micrograms iv) in nine subjects (two control patients, five patients with hypothyroidism and two patients with hyperthyroidism), NT levels decreased independently of the endocrine status from mean values of 13.4 +/- 8.4 at basal level to 7.3 +/- 0.8 fmol/ml 30 min after injection (p < 0.01 on paired percentage decrease values). These data suggest that plasma NT levels in humans depend upon the pituitary-thyroid status and indicate that TRH could exert a negative regulation on circulating NT levels.
 ...
PMID:Plasma neurotensin levels in humans: relation to hormone levels in diseases involving the hypothalamo-pituitary-thyroid axis. 758 81

Liver affects the release and clearance of many hormones, but the interactions between gastrointestinal peptides and liver function are obscure. Aim of this study was to evaluate plasma concentrations of gastrointestinal peptides during acute hepatic cytonecrosis and during liver regeneration in man. The study was performed in ten patients with viral hepatitis (8 virus A, 2 virus B) in the acute phase (alanine transaminase = 3073 +/- 739 U/L; mean +/- SEM), and at days 7, 45 and 52 after the initial evaluation, during clinical and biochemical recovery (52nd day, alanine transaminase = 77 +/- 26). Plasma concentrations of the following hormones were evaluated by radioimmunoassay: glucagon, insulin, gastrin, vasoactive intestinal peptide, bombesin, neurotensin, cholecystokinin, secretin and motilin. Only serum bombesin and cholecystokinin were significantly (p < 0.01) increased in the acute phase of hepatitis (bombesin: 138 +/- 21 pg/ml; cholecystokinin: 57 +/- 7 pg/ml); they returned to normal values during convalescence (bombesin: 60 +/- 8; cholecystokinin: 31 +/- 4). During hepatocellular necrosis, plasma concentrations of cholecystokinin and bombesin, which are both cellular growth factors and regulatory signals of food introduction and satiety state, were increased by 83% and 130%, respectively. Increase of these hormones may cause the dyspepsia and lack of appetite that characterizes the initial phase of acute viral hepatitis.
 ...
PMID:Gastrointestinal peptide hormones in acute viral hepatitis. 878

The present study investigated a possible relationship between plasma neurotensin (NT) and serum growth hormone (GH) levels after GH-stimulation provocative tests in humans. Samples were obtained from twelve prepubertal children and sixteen normal adult volunteers. Basal plasma NT levels were higher in children with growth delay (19.02 +/- 4.01 fmol/ml) (mean +/- SEM) than in normal adults (6.13 +/- 1.1 fmol/ml) (p < 0.001). Basal GH levels in children (1.52 +/- 0.06 ng/ml) were not different from those in adults (0.60 +/- 0.41 ng/ml). After stimulation of GH secretion, NT values decreased when GH peaked, and increased when GH levels diminished. These data suggest that plasma NT levels may be involved in the regulation of GH secretion, as a peripheral signal, probably through modulation of somatostatin release from the median eminence.
 ...
PMID:Plasma neurotensin levels in prepubertal children and adults: possible involvement in the regulation of growth hormone secretion. 982 12

Xenin is a 25-amino-acid peptide extractable from mammalian tissue. This peptide is biologically active. It stimulates exocrine pancreatic secretion and intestinal motility and inhibits gastric secretion of acid and food intake. Xenin circulates in the human plasma after meals. In this study, the cellular origin of xenin in the gastro-entero-pancreatic system of humans, Rhesus monkeys, and dogs was investigated by immunohistochemistry and immunoelectron microscopy. Sequence-specific antibodies against xenin detected specific endocrine cells in the duodenal and jejunal mucosa of all three species. These xenin-immunoreactive cells were distinct from enterochromaffin, somatostatin, motilin, cholecystokinin, neurotensin, and secretin cells, and comprised 8.8% of the chromogranin A-positive cells in the dog duodenum and 4.6% of the chromogranin A-positive cells in human duodenum. In all three species, co-localization of xenin was found with a subpopulation of gastric inhibitory polypeptide (GIP)-immunoreactive cells. Immunoelectron microscopy in the canine duodenal mucosa demonstrated accumulation of gold particles in round, homogeneous, and osmiophilic secretory granules with a closely adhering membrane of 187 +/- 19 nm diameter (mean +/- SEM). This cell type was found to be identical to the previously described canine GIP cell. Immunocytochemical expression of the peptide xenin in a subpopulation of chromogranin A-positive cells as well as the localization of xenin immunoreactivity in ultrastructurally characterized secretory granules permitted the identification of a novel endocrine cell type as the cellular source of circulating xenin.
 ...
PMID:Localization of xenin-immunoreactive cells in the duodenal mucosa of humans and various mammals. 1110 30


<< Previous 1 2 3 Next >>