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)

Thyrotrophin-releasing hormone (TRH) stimulates GH secretion in domestic fowl by actions at pituitary and central nervous system sites. The possibility that this central action might be mediated by hypothalamic catecholamines or indoleamines was therefore investigated. When TRH was administered into the lateral ventricles of anaesthetized fowl the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC, a metabolite of dopamine (DA)) in the medial basal hypothalamus (MBH) was increased within 20 min. The concentrations of MBH noradrenaline (NA), DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were, however, unaffected by the intra-cerebroventricular (i.c.v.) administration of TRH, although the MBH concentrations of somatostatin and TRH were concomitantly reduced. A rapid increase in DA release into MBH extracellular fluid and its metabolism to DOPAC was also observed after i.c.v. or i.v. administration of TRH, in birds in which the MBH was perfused in vivo with Ringer's solution. Microdialysate concentrations of NA, 5-HT and 5-HIAA were not, however, affected by central or peripheral injections of TRH. Diminished GH responses to i.v. TRH challenge occurred in birds pretreated with reserpine (a catecholamine depletor), alpha-methyl-paratyrosine (a DA synthesis inhibitor) and pimozide (a DA receptor antagonist). These results therefore provide evidence for the involvement of a hypothalamic dopaminergic pathway in the induction of GH release following the central or peripheral administration of TRH. In contrast with its inhibitory actions at peripheral sites, DA would appear to have a central stimulatory role in regulating GH release in birds.
 ...
PMID:Thyrotrophin-releasing hormone-induced growth hormone secretion in domestic fowl: concomitant stimulation of dopamine turnover in the medial basal hypothalamus. 822 31

Scintigraphy with iodine-123 or indium-111 labelled somatostatin analogue (octreotide) was performed in 52 patients diagnosed as, suspected of, or at risk of having carcinoid tumours. In 32 of 37 (86%) patients in whom histologically proven carcinoids were still present, known tumour sites were visualized. Using 123I-coupled octreotide, 24 of 40 (60%) known extrahepatic sites were visualized, whereas all of 12 (100%) extrahepatic lesions were visualized after injection of 111In-coupled octreotide. Known liver metastases were not distinctly visualized with octreotide scintigraphy in 12 of 24 patients. In all but two of these cases, an even distribution of radioactivity in the liver was observed. This is most probably due to the fact that these liver metastases accumulated about as much radioactivity as does normal liver tissue. Previously unsuspected localizations or sites not recognized with other imaging techniques were found in 20 of the 37 patients. In 3 of 11 patients who were thought to have been surgically cured, and in 4 of 4 patients who were suspected of having carcinoids, octreotide scintigraphy showed abnormal accumulation of radioactivity. Histological or radiological evidence that additional sites noticed on octreotide scintigrams indeed represented tumour tissue was obtained in ten patients. Visualization of the carcinoids did not depend on the site of the tumour or on the presence or absence of hormonal hypersecretion, as measured by urinary 5-hydroxyindoleacetic acid and serum alpha-subunit concentrations. Apart from its use for tumour localization, octreotide scintigraphy, in consequence of its ability to demonstrate somatostatin receptor positive tumours, could be used to select those patients with the carcinoid syndrome who are likely to respond favourably to octreotide treatment.
 ...
PMID:Somatostatin analogue scintigraphy in carcinoid tumours. 849 Dec 20

There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).
 ...
PMID:Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease--effect of L-Dopa. 881 4

Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.
 ...
PMID:Somatostatin receptor imaging: predictive and prognostic considerations. 881 70

We have measured the concentrations of substance P, somatostatin, homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of six patients suffering from narcolepsy and 12 age- and gender-matched controls using high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). Substance P and somatostatin were significantly decreased in our patients compared to controls (36.9 +/- 9.1 fmol/ml versus 52.5 +/- 9.9 fmol/ml, P < 0.05 and 30.3 +/- 7.8 fmol/ml versus 43.9 +/- 9.8 fmol/ml, P < 0.05, respectively). 5-HIAA (P < 0.05) and VMA (P < 0.05) were also significantly decreased. HVA was significantly increased (P < 0.01). The CSF concentrations of substance P and somatostatin correlated with the clinical parameters duration of disease (r = -0.68, P < 0.05 and r = -0.72, P < 0.05, respectively) and severity of cataplectic symptoms (r = -0.71, P < 0.05 and r = -0.78, P < 0.01). In addition, substance P correlated with the intensity of sleepiness and the frequency of day-sleep attacks (r = -0.69, P < 0.05 and r = -0.68, P < 0.05, respectively). Substance P affects the amount of dopamine release in the nigra-striatal region, and decreased amounts could contribute to the pathogenesis of narcolepsy. Reduced levels of substance P, which affects serotonin release, may be responsible for diminished release of serotonin which in turn could affect sleep cycles. Because somatostatin affects motor behavior through dopaminergic mechanisms and since the levels of somatostatin correlate with the intensity of cataplectic symptoms, we speculate that an interaction between somatostatin and dopaminergic neurons plays a role in the pathogenesis of narcolepsy.
 ...
PMID:CSF substance P somatostatin and monoaminergic transmitter metabolites in patients with narcolepsy. 894 37

With passive avoidance (PA), Morris water maze (WM) and eight-arm radial maze tasks, we evaluated the memory-enhancing action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a compound which we have found through rational drug screening based on our hypothesis that penile erection is a valid predictor of central cholinergic activation. Memory performance in the tasks was impaired in aged (24- to 26-months-old) rats as well as in rats with nucleus basalis magnocellularis lesions. Scopolamine (1 mg/kg i.p.) treatment induced memory impairment in PA and WM; treatment with cysteamine (200 mg/kg s.c.) induced memory impairment in PA but not in WM, whereas fimbria fornix lesioning affected the rats in the opposite manner. FK960 (0.1-10 mg/kg i.p.) ameliorated all the memory impairments except those induced by cysteamine or fimbria fornix lesion, and the dose-response curves were bell shaped with maximal response at 1 to 3.2 mg/kg. The effects of FK960 on the scopolamine-induced memory impairment in the PA and/or WM were abolished by cysteamine (200 mg/kg s.c.), dl-p-chlorophenylalanine methyl ester hydrochloride (150 mg/kg i.p. for 3 days) or raphe lesioning, but not by neonatal 6-hydroxydopamine (35 micrograms/head) treatment. Neurochemical analysis revealed that cysteamine and raphe lesions reduced brain somatostatin and serotonin contents, respectively. The treatment with FK960 (0.32-320 mg/kg p.o.) dose-dependently increased both serotonin and 5-hydroxyindoleacetic acid levels in the brain areas examined and significantly increased hippocampal somatostatin contents at the smaller doses. From these results, we conclude that FK960 ameliorates cognitive dysfunction through an activation of the somatostatinergic-serotonergic link.
 ...
PMID:FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action. 896 37

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early onset form of Alzheimer's disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.
 ...
PMID:Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients. 899 49

In 21 patients suffering from Binswanger's disease (BD) and in 53 patients suffering from Alzheimer's disease, we measured cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The patients were classified into three stages of intellectual deterioration according to the global deterioration scale (GDS). Levels of SLI were significantly decreased in BD in general and in SDAT patients with severe dementia (GDS 7), compared to a control group (BD overall 19.7 +/- 11.6 fmol/ml, SDAT 18.6 +/- 7.9 vs. 30.5 +/- 8.6 fmol/ml in controls, p < 0.01 for both). In SDAT patients, SLI levels correlated with dementia scores (r = -0.65, p < 0.05), but not in BD. HVA levels were decreased significantly in SDAT and BD patients with severe dementia (SDAT 273.5 +/- 138.7, BD 224.3 +/- 69.9 vs. 364.9 +/- 103.8 nmol/ml, p < 0.01 in controls, p < 0.05 for both). In BD patients with light dementia (GDS 2-4), HVA levels were significantly elevated (p < 0.05). In BD, HVA levels correlated with dementia (r = -0.59, p < 0.01). 5-HIAA was significantly elevated in BD patients with light dementia (p < 0.05). Qualitative and quantitative changes in the molecular forms of SLI are compatible with a dysregulated posttranslational processing SDAT and BD. We also observed significant correlations between SLI, 5-HIAA and HVA in BD indicating a neurochemical heterogeneous and generalized process affecting several transmitter systems and functions. In summary, our study shows that despite their quite different neuropathology, SDAT and BD do not differ fundamentally in their neurochemical profile.
 ...
PMID:Neurochemical differences in the CSF between Binswanger's and Alzheimer's disease. 899 50

The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydroxphenylacetic acid (DOPAC), and the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control subjects, aged 16-75 years. After correcting for postmortem interval, significant decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA concentrations were obtained with advancing age. The involvement of the monoaminergic system in several functional abnormalities appearing in senescence is suggested. Furthermore, evidence is given of the participation of the peptidergic systems in the aging process.
 ...
PMID:Brain monoaminergic and neuropeptidergic variations in human aging. 902 65

Cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in 21 patients with Binswanger's dementia (BD). Patients were classed into three stages of intellectual deterioration according to the Global deterioration scale (GDS). Levels of SLI were significantly decreased in patients suffering from BD, compared to a control group (19.7 +/- 11.6 fmol/ml vs. 30.5 +/- 8.6 fmol/ml, P < 0.01). There was no correlation with dementia scores (r = 0.34, P = 0.51). The observed qualitative and quantitative changes in the molecular pattern of SLI suggest that occurrence of a dysregulated posttranslational processing in patients with BD. Whereas 5-HIAA levels were not significantly changed in patients with BD, HVA was significantly increased in mild to moderate dementia (GDS 2-4) and significantly decreased in severe cases (GDS 7) (224.3 +/- 69.9 nmol/ml vs. 364.9 +/- 103.8 nmol/ml, P < 0.01); this correlated with dementia scores (r = -0.59, P < 0.01). The existence of significant correlations between SLI, 5-HIAA and HVA in BD point to a heterogeneous and generalized neurochemical process affecting several transmitter systems and functions.
 ...
PMID:Somatostatin, its molecular forms and monoaminergic transmitter metabolites in Binswanger's disease. Neurochemical-neuropathological considerations. 911 48


<< Previous 1 2 3 4 5 6 7 Next >>