Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
...
PMID:Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. 768 63

Series of recombinant plasmids for expression of the synthetic gene somatostatin-14 (SST) as a fusion protein were obtained. The somatostatin gene was fused to chloramphenicol acetyltransferase (cat) or its deleted variant genes. Both parts of the resultant fusion protein were joined through a Met residue. The hybrid gene was expressed under the control of the cat gene promoter (Pcat), the tryptophan operon promoter (Ptrp) or the promoter of bacteriophage T5 (PT5). These fusions gave insoluble polypeptide products amounting from 5-10% of the total cellular protein under constitutive biosynthetic conditions (Pcat) to 5-30% upon induction (Ptrp, PT5). A correlation between the efficiency of expression and the length of cat, the power of the promoter used and the absence or presence of transcription terminators, was studied. The scheme for SST isolation from bacterial cells was developed. SST was liberated from the fused polypeptide by treatment with cyanogen bromide and purified to homogenity by a combination of chromatographic steps: gel filtration, ion-exchange and rpHPLC. The renaturated recombinant SST showed specific biological and immunological activities and had 98% purity. The yield was 1 mg of the purified cyclic SST/1 culture of E.coli.
...
PMID:[Genetic engineering in the bacterial synthesis of somatostatin]. 774 53

The effect of somatostatin (SS) on adrenocorticotrophic hormone (ACTH) secretion from COR-L103 cells derived from a human small cell lung carcinoma was examined. SS at 1 microM had no effect on ACTH secretion from the cells on either short-term or long-term incubation. Studies by the reverse transcription-polymerase chain reaction (RT-PCR) showed that mRNA transcripts of the somatostatin receptor (SSTR) 2, SSTR3 and SSTR4 genes were present in COR-L103 cells. Extra bands were obtained by PCR-single strand conformation polymorphism (SSCP) analysis of the SSTR2 gene Sequence analysis of the SSTR2 gene demonstrated one point mutation in codon 188 of TGG for tryptophan to TGA for a stop codon causing loss of 182 C-terminal amino acid residues of SSTR2. The nucleotide sequences of the SSTR3 and SSTR4 genes in COR-L103 cells were normal. Binding studies using 125I-Tyr11-SS-14 showed specific affinity binding sites on COR-L103 cells and mouse pituitary tumor AtT-20 cells. Octreotide acetate suppressed the binding of 125I-Tyr11-SS-14 to these two cell lines, but the Kd of COR-L103 cells (160 nM) was 60-fold higher than that of AtT-20 cells (2.6 nM). Affinity cross-linking studies using 125I-Tyr11-SS-14 gave three bands of 72 KDa, 55 KDa and 32 KDa from AtT-20 cells, but only two bands of 55KDa and 32kDa from COR-L103 cells. These findings suggest that SSTR2 is not expressed in the plasma membranes of COR-L103 cells due to a point mutation, but that this may have no influence on the effect of SS on ACTH secretion.
...
PMID:Point mutation of the somatostatin receptor 2 gene in the human small cell lung cancer cell line COR-L103. 776 54

The neuropharmacologic basis of infantile spasms and the mechanism by which adrenocorticotropic hormone (ACTH) exerts its therapeutic effects are unknown. This is a critical review of cerebrospinal fluid neurotransmitters or their metabolites in infantile spasms before and during treatment with ACTH, and of clinical drug trials with drugs acting on neurotransmission. Cerebrospinal fluid studies have shown lower gamma-aminobutyric acid (GABA), ACTH, and 5-hydroxyindoleacetic acid concentrations in patients with infantile spasms compared to controls, elevated lysine and glutamate, variable or no differences in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, norepinephrine, corticotropin-releasing hormone, and beta-endorphin. Chronic treatment with ACTH in infantile spasms reduces cerebrospinal fluid GABA, beta-endorphin, and somatostatin, increases norepinephrine and tyrosine, and has variable or no effect on homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, histamine, and tryptophan. Small therapeutic trials with drugs that act through different neurotransmitters such as methysergide, alpha-methylparatyrosine, various benzodiazepine agonists, and vigabatrin lend some support to a role for GABA and monoamines in infantile spasms. These data, though promising, provide only a hint of potential neurotransmitter disturbances, and more basic and clinical data are needed.
...
PMID:Putative neurotransmitter abnormalities in infantile spasms: cerebrospinal fluid neurochemistry and drug effects. 791 15

The possible occurrence of adrenergic and non-adrenergic vasoconstrictor mechanisms has been studied in human nasal mucosa biopsies. The tissue contractions (reflecting vascular tone variation) in response to exogenous noradrenaline (NA), neuropeptide Y (NPY) and somatostatin (SOM) were measured in vitro. Dose-dependent contraction of the nasal mucosa was observed for the three agents studied and the rank order of their vasoconstrictive potency was NA > SOM > NPY. On a molar basis NPY showed an 80% less potent vasoconstrictive activity than SOM. Pretreatment with the alpha-adrenoceptor antagonist phenoxybenzamine (10(-6) M) almost completely abolished the vasoconstrictive response to NA, whereas the effects of NPY and SOM remained intact. The responses to SOM were significantly reduced after pretreatment with high dose of the competitive SOM-antagonist analog cyclo(7-aminoheptanoyl-PHE-D-TRP-LYS-THR[BZL]). When SOM was administered simultaneously with NA, the contractile response was significantly reduced as compared to the effect of NA alone. In contrast, concomitant administration of NPY and NA potentiated the vasoconstrictive effect of NA. The present data suggest that both adrenergic and non-adrenergic vasoconstrictor mechanisms are present in the human nasal mucosa vascular bed. Furthermore, NPY and SOM may act as modulators of the NA-induced vasoconstrictive effects.
...
PMID:Adrenergic and non-adrenergic vasoconstrictor mechanisms in the human nasal mucosa. 810 Jun 40

Cranial radiation for childhood cancer can cause growth hormone deficiency (GHD), usually due to hypothalamic rather than pituitary dysfunction. To investigate whether this hypothalamic dysfunction is secondary to altered neurotransmitter input from other brain centers, we used neurotransmitter-excitatory substances to study the GH secretory response in 17 children who had received 12 to 60 Grey (Gy) to the cranium and 40 short children with normal endocrine function. As expected, the irradiated children had decreased mean GH secretion in response to insulin-induced hypoglycemia and arginine infusion, and decreased mean 24 hour GH concentrations, compared to the control group. In contrast, the two groups had similar GH secretory responses to GHRH stimulation and somatostatin suppression. Assessment of neurotransmitter pathways in the irradiated children revealed significantly lower mean peak GH concentrations in response to 5 of the 6 substances tested compared to control children: alpha-adrenergic stimulation (clonidine), beta-adrenergic blockade (propranolol), cholinergic stimulation, dopaminergic stimulation (L-dopa), and GABA-ergic stimulation (valproic acid). Results of serotonergic stimulation (L-tryptophan) were not statistically significant. Eleven patients who had abnormal GH secretion underwent 4 or more tests with neurotransmitter-stimulatory agents; 3 patients had peak GH concentrations of < 2.5 micrograms/l to all tests, whereas 4 patients had a peak GH concentration of > or = 7 micrograms/l to one or more tests but < 5 micrograms/l to one or more other tests. These observations suggest that radiation damage may sometimes spare growth hormone-releasing hormone (GHRH) and somatostatin secretion while affecting neurotransmitter pathways. We postulate that the hierarchy of sensitivity to radiation damage may be hypothalamic and extra-hypothalamic neurotransmitters > hypothalamic GHRH and/or somatostatin secretion > pituitary GH secretion.
...
PMID:Neurotransmitter control of growth hormone secretion in children after cranial radiation therapy. 810 3

To determine the component(s) of dietary protein that regulates GH-releasing factor (GRF) synthesis, we measured hypothalamic prepro-GRF mRNA by solution hybridization/nuclease protection analysis in food-deprived rats refed protein-free diets (PF) supplemented with individual amino acids. Adult male Sprague-Dawley rats were allowed free access to food (Fed), food deprived for 72 h (FD), or FD then refed for 72 h with a normal (NF) diet, a protein-free (PF) diet, or PF diets containing tyrosine, tryptophan (Trp), glutamic acid, or histidine (His). Food-deprived rats displayed the expected 80% reduction in hypothalamic prepro-GRF mRNA. Upon refeeding, levels were normalized in rats refed a normal diet, but not in those refed a PF diet alone or with tyrosine, Trp, or glutamic acid. In contrast, prepro-GRF mRNA was restored to 70% of Fed values by a PF diet with His. Supplementing a PF diet with His was sufficient to maintain hypothalamic prepro-GRF mRNA expression, as 3 days of feeding replete rats with PF diet or PF diet with added Trp resulted in a 50% reduction in prepro-GRF mRNA, whereas levels were reduced 25% by feeding animals a PF diet with His. Groups of rats allowed free access to food were treated for 72 h with two daily injections of 100 mg/kg alpha-fluoremethylhistidine, a specific irreversible inhibitor of histidine decarboxylase, to determine if the effect of His on prepro-GRF mRNA depended on neural conversion to histamine. alpha-Fluoremethylhistidine-treated rats showed a 40% reduction in hypothalamic prepro-GRF mRNA, with no concomitant change in preproneuropeptide-Y or preprosomatostatin. These data indicate that decreased hypothalamic prepro-GRF mRNA in FD rats is due in part to the lack of dietary and provide clear evidence for a role of the histaminergic neural system in the regulation of hypothalamic GRF expression.
...
PMID:Regulation of hypothalamic preprogrowth hormone-releasing factor messenger ribonucleic acid expression in food-deprived rats: a role for histaminergic neurotransmission. 810 51

The studies were performed on cultured TT cells originating from human thyroid medullary carcinoma (i.e., from parafollicular cells of the thyroid). The amount of released calcitonin was dependent upon calcium level in the medium. Moreover, calcitonin secretion might be regulated by medium supplementation with polypeptide hormones. Somatostatin inhibited while glucagon and pentagastrin stimulated calcitonin secretion to t he medium. Calcitonin secretion was also influenced by biogenic amines and their precursors. Dihydroxy-1-phenylalanine and serotonin augmented while 5-hydroxy-1-tryptophan and dopamine inhibited calcium secretion. This, calcitonin secretion may be controlled by different substances present in the healthy organism. This points to a complex control of calcium ion level in the blood.
...
PMID:Regulation of calcitonin secretion by thyroid parafollicular cells in vitro. 861 73

S-4-methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups of the tert butyl type and S-Trt by treatment with 0.5-1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr1-somatostatin on 2-chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively used for amino acid side-chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM-TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions.
...
PMID:Synthesis of the very acid-sensitive Fmoc-Cys(Mmt)-OH and its application in solid-phase peptide synthesis. 874 Sep 63

Hormonal overproduction is a significant problem in patients with disseminated midgut carcinoid tumors. Serotonin (5-HT) is one major product secreted from such tumors and the urinary excretion of its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) serves as an important tumor marker. The present study aimed at elucidating mechanisms of tryptophan metabolite secretion to facilitate the treatment of the carcinoid syndrome. When midgut carcinoid tumors were studied in primary cell cultures, several similarities with adrenergic neurons could be demonstrated. A marked dose-dependent depletion of intracellular 5-HT could be induced by reserpine, and monoamine oxidase-activity was revealed both in functional studies and by immunocytochemistry. Differences between tumors in the ratios of tryptophan metabolites released indicated that enzymes for synthesis and degradation of 5-HT were individually expressed. Treatment with the somatostatin analogue octreotide or with dexamethasone decreased the extracellular levels of tryptophan metabolites, but the mechanisms were partly different. In some tumors octreotide also decreased the synthesis of 5-HT, while dexamethasone markedly increased the intracellular 5-HIAA levels. It is of clinical interest to further elucidate these mechanisms, since the two drugs may have complementary actions in carotid crisis reactions.
...
PMID:Secretory patterns of tryptophan metabolites in midgut carcinoid tumor cells. 923 53


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

---