Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization was used to study the expression of prepro-neuropeptide Y (NPY), preprosomatostatin (SOM), preprotachykinin (PPT) and preprocholecystokinin (CCK) mRNA in caudate-putamen and frontoparietal cortex of rat brain with unilateral lesion of midbrain dopamine neurons. Neurons expressing NPY and SOM mRNA showed a similar distribution and the expression of both NPY and SOM appears to be regulated by dopamine in a similar fashion. Following a dopamine deafferentation, the numerical density of both NPY and SOM mRNA producing neurons almost doubled in the lesioned caudate-putamen with no change in the average grain density over positive neurons. Hence, in the intact caudate-putamen dopamine appears to suppress expression of these two neuropeptide genes leading to an activation of both NPY and SOM mRNA expression in many non- or low-expressing neurons when the level of dopamine is decreased. In the fronto-parietal cortex, on the other hand, dopamine appears to stimulate NPY and SOM gene expression. Thus, in the absence of dopamine about half of the NPY positive neurons disappeared. However, for SOM the number of positive neurons did not change, but rather most positive neurons appeared to have down-regulated their SOM mRNA expression. No evidence was found for a change in CCK mRNA expression by the dopamine deafferentation, while PPT mRNA expression decreased in the deafferented caudate-putamen. Consequently, dopamine exerts dissimilar effects on the expression of different neuropeptide genes, that in turn do not respond in the same way in different brain regions.
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PMID:Neuropeptide gene expression in brain is differentially regulated by midbrain dopamine neurons. 238 50

Two calcium-activated neutral proteases (CAPI & II) were purified from human skeletal muscle by anion exchange, gel filtration and affinity (antipain-Sepharose and Blue Ultrogel A4R) chromatography. The enzymes were homogenous as judged by polyacrylamide gel electrophoresis, and have similar properties with the exception of the Ca2+ concentration required for optimum activity (CAP I = 0.1 mM; CAP II = 1 mM). Both enzymes hydrolysed a wide variety of neuropeptides. In six cases, the products were separated and identified by hplc and amino acid analysis. Neurotensin was hydrolysed at Tyr3-Glu4; dynorphin1-13 at Arg8-Arg9; LH-RH at Gly6-Leu7; CCK-8 at Phe8-NH2, substance-P at Met10-NH2; somatostatin at Thr10-Phe11. Although differences in the rates of neuropeptide degradation were noted for the two CAP's the specificity was the same for these six peptides. It is suggested that conformational requirements may be more important than side chains adjacent to the cleavage site in directing the specificity of CAP.
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PMID:Specificity of neuropeptide degradation by two calcium-activated neutral proteases from human skeletal muscle. 241 Jul 57

The presence and distribution of regulatory peptides in nerves and endocrine cells of the stomach, intestine and rectum of a urodele amphibian, the mudpuppy, Necturus maculosus, was studied immunohistochemically in sections or whole-mount preparations of the gut wall. The effect of the occurring peptides on gut motility was studied in isolated strip preparations of circular and longitudinal smooth muscle from different parts of the gut. Bombesin-, neurotensin-, substance P- and VIP-like immunoreactivity was present in abundant nerve fibres in the myenteric plexus of both stomach, intestine and rectum. Single fibres or bundles were present in the circular muscle layer and in a well-developed deep muscular plexus in the intestine and rectum. Immunoreactive nerve cells were found in the myenteric plexus of the stomach, intestine (neurotensin only) and rectum. Gastrin/CCK-like immunoreactivity was observed only in a few fibres in stomach and rectum. Endocrine cells containing bombesin-, met-enkephalin-, gastrin/CCK-, neurotensin-, somatostatin- or substance P- like immunoreactivity were present in the mucosa. The effect of bombesin was an inhibition of the rhythmic activity in circular muscle preparations and in longitudinal muscle from the rectum, while longitudinal muscle from the stomach usually responded with a weak increase in tonus. Neurotensin, like-bombesin, was inhibitory on the spontaneous rhythmic activity of circular muscle throughout the gut, while the effect on longitudinal muscle was an increase in tonus. Met-enkephalin and substance P increased the tonus of all types of preparations, and often, in addition, initiated a rhythmic activity superimposed on this maintained tonus. VIP had a general inhibitory effect on the preparations, decreasing tonus and/or abolishing rhythmic activity. It is concluded that bombesin-, neurotensin-, substance P- and VIP-like peptides are present in nerves throughout the urodele gut and may have physiological functions in regulating the motility of the gut. The gastrin/CCK-like peptide present in nerves of the stomach and rectum may affect the function of these parts of the gut. The regulatory peptides present in endocrine cells may, perhaps with the exception of the somatostatin-like peptide, affect the motility humorally.
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PMID:Neuropeptides in the gastrointestinal canal of Necturus maculosus. Distribution and effects on motility. 241 14

To further elucidate the pathophysiological role of peptide hormones in duodenal ulcer (DU) disease, several endocrine, paracrine and neurocrine peptides were determined radioimmunologically in biopsies of gastroduodenal mucosa obtained endoscopically in 8 subjects without upper gastrointestinal disease, and in 8 duodenal ulcer patients. The DU patients had a BAO of 6.6 +/- 1.9 and a PAO of 41.8 +/- 6.1 mEq/h. In DU patients, a lack of the acid and gastrin-release inhibiting agent somatostatin was found neither in antral nor in fundic mucosa (185 +/- 60 vs 83 +/- 19 pmol/g tissue wet weight in controls). Basal and peak acid outputs of DU patients were positively correlated with fundic somatostatin concentrations (p less than 0.01). While gastrin levels were not significantly elevated in the antrum of DU patients, the mucosal content of potentially releasable gastrin of the duodenal bulb and the descending duodenum was higher than in controls (p less than 0.01). In the whole duodenum, CCK-like immunoreactivity was also more abundant in DU patients than in controls, whereas GIP and motilin did not exhibit characteristic profiles. Presumably as a reactive phenomenon, the mucosal levels of the peptidergic neurotransmitters VIP and substance P were markedly increased in the proximal duodenum of DU patients.
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PMID:Gastroduodenal mucosal hormone content in duodenal ulcer disease. 241 97

Twenty medullary carcinomas of the thyroid gland were examined for the presence of immunoreactive calcitonin, thyroglobulin, glucagon, keratin, gastrin/CCK, carcinoembryonic antibody (CEA), insulin, serotonin, adreno-corticotropic hormone (ACTH), prostatic acid phosphatase, and somatostatin using the immunoperoxidase peroxidase-antiperoxidase technique. In addition, they were stained with mucicarmine, alcian blue/periodic acid-Schiff (PAS), Grimelius, Congo red, crystal violet, and Fontana-Masson stains. Calcitonin-immunoreactive cells were absent in one tumor and present in 19 tumors (95%). Thyroglobulin was present in seven tumors (35%). Twenty tumors contained CEA-immunoreactive cells (100%). Fourteen cases were immunoreactive to serotonin (70%) and 12 were positive for somatostatin (60%). Glucagon- and gastrin/CCK-immunoreactive cells were found in two cases each (10%). Four tumors (20%) contained ACTH-immunoreactive cells and three cases (15%) were positive for prostatic acid phosphatase. Five cases (25%) contained keratin-immunoreactive cells. One case was immunoreactive to insulin (5%). Grimelius-positive cells were present in 19 of the cases (95%). Mucin-containing cells were present in 65% of the cases. The validity of the immunocytochemical localizations was tested by specific absorption of each antibody with the corresponding antigen. The demonstration of immunoreactivity for multiple antigens in each of the 20 cases suggests that the origin of medullary thyroid carcinomas is from a neuroendocrine cell potentially capable of producing numerous hormone substances. In addition, as the neoplastic cells in 35% of the tumors contained hormonal substances as well as thyroglobulin, it is suggested that papillary or follicular tumors mixed with a neuroendocrine component exist more commonly than previously suspected. Finally, psammoma bodies might be present in pure medullary carcinoma of the thyroid gland.
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PMID:Medullary carcinoma of the thyroid gland. Clinical, pathological, and immunohistochemical features with review of the literature. 241 97

A whole mount immunofluorescence method was used for the localization of immunoreactivity (IR) to four regulatory peptides and the bioamine serotonin in the nervous system of Stenostomum leucops (Turbellaria, Platyhelminthes). The flatworm S. leucops belongs to the taxon Catenulida which, according to the new phylogenetic system by Ax [2], forms a key group between the coelenterates and more advanced flatworm species. Positive IR was obtained using antisera against FMRF-amide, beta-endorphin, growth hormone releasing factor (GRF), substance P, and serotonin. The distribution patterns of these neuropeptide-like immunoreactivities differ significantly from each other. Antisera against Leu-enkephalin, bovine pancreatic polypeptide (BPP), bombesin, cholecystokinin (CCK-8), neurotensin, somatostatin, growth hormone (GH), secretin, and neurophysin II gave negative results. This primitive flatworm shows similarities with hydra in the lack of IR to anti-somatostatin, anti-Leu-enkephalin, and anti-BPP. These antisera give positive IR in more advanced flatworm species, indicating a later convergent evolution of vertebrate-like peptides within the phylum Platyhelminthes.
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PMID:Neuropeptides in a microturbellarian--whole mount immunocytochemistry. 242 Dec 67

The contribution of the myenteric plexus in the mechanical responses of rat jejunal longitudinal muscle produced by several enteric nerve substances was evaluated. The myenteric plexus of a segment of rat jejunum was destroyed by serosal application of benzalkonium chloride (BAC). Fifteen days after BAC treatment, both the BAC-treated and an orad control jejunal segment were removed and the mechanical responses of the longitudinal muscle produced by the following substances were examined: substance P, acetylcholine (ACh), 5-hydroxytryptamine (5-HT), cholecystokinin octapeptide (CCK-8), norepinephrine, vasoactive intestinal peptide (VIP), bombesin, [Leu5]enkephalin and somatostatin. Our results indicate that: substance P and norepinephrine produce their mechanical responses by acting predominantly on the longitudinal smooth muscle; 5-HT, CCK-8, ATP, VIP and neurotensin act predominantly through the myenteric plexus; ACh possesses both direct and indirect actions; and because the responses to [Leu5]enkephalin, bombesin and somatostatin were equivocal, a conclusion as to their site of action could not be made with this preparation.
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PMID:Differentiation between myenteric plexus and longitudinal muscle of the rat jejunum as the site of action of putative enteric neurotransmitters. 243 41

Afferent perikarya in dorsal root ganglia (DRG) at the T13 and L1 segmental levels projecting to the rat ovary were identified by utilizing the fluorescent retrograde tracer true blue (TB). Subsequently, TB-labeled ovarian afferent perikarya in DRG were examined for vasoactive intestinal polypeptide (VIP), substance P (SP), cholecystokinin-8 (CCK-8), neuropeptide Y (NPY), and somatostatin (SOM) immunoreactivity and for the presence of fluoride-resistant acid phosphatase (FRAP) enzyme activity. Of the ovarian afferent perikarya at the T13 and L1 segmental levels, 20.5% displayed VIP immunoreactivity, 23.8% displayed SP immunoreactivity, and 43.1% were immunoreactive for CCK-8. No ovarian afferent perikarya contained SOM or NYP immunoreactivity or FRAP activity. It is suggested that different neuropeptides may participate in modulation of specific ovarian functions.
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PMID:Neuropeptides in sensory perikarya projecting to the rat ovary. 244 98

We have examined the direct effect of somatostatin (SRIF) on basal and stimulated amylase release from guinea pig pancreatic acini using the in vitro method of continuous perifusion. The optimal conditions of flow rate, chamber size, acinar cell volume per chamber, and period of secretagogue infusion were defined for the perifusion system. The kinetic profile of amylase release in response to cholecystokinin-octapeptide (CCK-8), vasoactive intestinal peptide (VIP), and SRIF was studied. Under optimal conditions, the acini were found to remain equally responsive to an ED50 dose of CCK-8 (0.5-0.8 nM) for 12 h of perifusion. The duration of amylase response to any given dose of CCK-8, given for the optimal period of 5 min, was 80-100 min. The total amylase released minus the basal release divided by 90 min (delta response) in response to the maximum effective (Maxeff) dose of CCK-8 (100 nM) was 14,667 +/- 1,433 U/l (amounting to a 10-fold increase compared with basal values). When compared with the amount of total delta amylase released in response to the Maxeff dose of CCK, the total amylase released in response to the Maxeff doses of SRIF (1 microM) and VIP (10 nM) was 10-21% and 51-59%, respectively. SRIF (100 nM) significantly decreased VIP- (0.1-1.0 nM) stimulated amylase release by 45-70% in the perifusion method of study but had no significant effect on the CCK-stimulated amylase release. This suggests that the perifusion method can be used for investigating the mechanism of SRIF-mediated inhibition of VIP effects on amylase release in an in vitro system.
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PMID:Somatostatin inhibits VIP-stimulated amylase release from perifused guinea pig pancreatic acini. 245 Apr 69

Exogenous galanin has been shown to suppress insulin secretion as elicited by a number of secretagogues such as glucose, arginine, tolbutamide, carbachol, and oral nutrients. To achieve further insight into the influence of galanin on the endocrine pancreas, we have investigated the effect of synthetic porcine galanin (a 200 ng bolus followed by constant infusion at a concentration of 16.8 ng/mL for 16 to 24 minutes) on unstimulated insulin, glucagon, and somatostatin release, as well as on the responses of these hormones to 1 nmol/L vasoactive intestinal peptide (VIP), 1 nmol/L gastric inhibitory peptide (GIP), 1 nmol/L 26 to 33 octapeptide form of cholecystokinin (8-CCK) or 10 nmol/L glucagon in the perfused rat pancreas. Galanin infusion reduced unstimulated insulin secretion by 60% without modifying glucagon and somatostatin output. Galanin also blocked insulin release elicited by VIP, GIP, and 8-CCK, it did not affect the glucagon responses to VIP and GIP, or the somatostatin responses to VIP, GIP, and 8-CCK. Finally, galanin inhibited the insulin output, but not the somatostatin release induced by glucagon. In conclusion, in the perfused rat pancreas, galanin appears to behave as a general inhibitor of insulin secretion. Since this neuropeptide does not modify glucagon or somatostatin release, a direct effect of galanin on the B-cell seems plausible.
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PMID:Effects of galanin on islet cell secretory responses to VIP, GIP, 8-CCK, and glucagon by the perfused rat pancreas. 245 42


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