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

Biologically active peptides and neurotransmitter substances were added to anterior pituitary cell cultures to examine the presence of corticotropin releasing factor (CRF)-like activity. Hypothalamic extract (HE) induced significant dose-related increase of ACTH, and the lowest effective dose was 0.01 HE/ml. Other tested substances including luteinizing hormone-releasing hormone, thyrotropin releasing hormone, melanocyte stimulating hormone release inhibiting factor, somatostatin, substance P, neurotensin, beta-endorphin. leu-enkephalin, met-enkephalin, bradykinin, norepinephrine, dopamine, serotonin, acetylcholine, histamine, gamma-amino butyric acid or gamma-hydroxy butyric acid showed no CRF-like activity. Relatively high doses of lysine vasopressin, arginine vasopressin and angiotensin II increased the release of ACTH in pituitary cell cultures, but the maximal ACTH response was markedly less than with HE. These results indicate that cultured anterior pituitary cells are sensitive and fairly specific in detecting CRF(s) comparing with other detecting procedures.
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PMID:Specificity of cultured anterior pituitary cells in detecting corticotropin releasing factor(s): the effect of biologically active peptides and neurotransmitter substances on ACTH release in pituitary cell cultures. 3 34

Several immunogold techniques were used to determine the ultrastructural localization of calcitonin gene-related peptide (CGRP), tachykinin, somatostatin, and gamma-amino-butyric acid (GABA) immunoreactivity in the dorsal horn of rat spinal cord. The immunocytochemical reactions were carried out directly on ultrathin sections from non-osmicated frozen tissue, non-osmicated low temperature-embedded (Lowicryl K4M) tissue, and osmicated epoxy-embedded material. Preservation of ultrastructural morphology and immuno-labeling efficiency were compared. Morphology of subcellular organelles was relatively good in ultra-thin frozen sections, which showed the highest immunoreactivity. However, only very small samples of tissue could be examined. Although there was relatively good immunolabeling in the Lowicryl K4M-embedded tissue, the ultrastructure of the neuropil, and particularly that of synapses, was poorly maintained. In contrast, the osmicated epoxy-embedded material offered optimal morphological preservation together with accurate subcellular localization of all antigens under study. The latter approach thus enabled clear visualization of CGRP, tachykinin, and somatostatin immunoreactivity restricted to large dense-cored vesicles (90-150 nm diameter) in many axonal and synaptic profiles in the superficial layers of the dorsal horn. CGRP- and tachykinin-positive profiles were also present in the tract of Lissauer. GABA immunoreactivity was present mainly in axons and terminals, and less frequently in somatic and dendritic profiles. In terminals, which often formed symmetrical synapses on immunonegative dendritic profiles, it was associated with small (30-60 nm diameter) clear vesicles and mitochondria. Double immunolabeling was possible on all preparations, but the osmicated, epoxy-embedded material clearly showed co-localization of peptides, especially of CGRP and tachykinins, within the same dense-cored vesicles in axonal fibers and/or terminals. On the other hand, peptide and GABA immunoreactivity were consistently seen in different nerve profiles. In a few cases, GABAnergic terminals were seen to synapse on tachykinin-positive fibers.
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PMID:Ultrastructural localization of neuropeptides and GABA in rat dorsal horn: a comparison of different immunogold labeling techniques. 256 4

Long-term ingestion of high fiber diets is associated with reduced glucose concentrations during fasting and improved glucose tolerance (KG) in humans. Our objective was to determine if the beneficial effects of fiber were attributable to increased production of short-chain fatty acid (SCFA) in the large intestine. Effects of SCFA on insulin sensitivity (SI), glucose effectiveness (SG), KG and baseline concentrations of glucose, insulin, glucagon and free fatty acids were examined in unfed 20-50 kg pigs (n = 6). Animals randomly received separate portal infusions (0.32 mL.min-1) of saline, acetic, propionic, and butyric acid solutions (0.01 mmol SCFA kg body weight-1.min-1) for 7-d periods. On d 7, somatostatin and tolbutamide modified frequently sampled intravenous glucose tolerance tests were performed. SI and SG were calculated using Bergman's Minimal-Model. KG was determined by regression of log glucose curve versus time. SI, SG and KG values did not differ among the treatments (P > 0.05). Baseline concentrations of glucose, insulin, glucagon and free fatty acids were unaffected by infusion treatment (P > 0.05). Our results suggest that SCFA delivery is not directly responsible for improvements in glucose metabolism observed with long-term ingestion of high fiber diets.
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PMID:Splanchnic infusions of short chain fatty acids do not change insulin sensitivity of pigs. 756 92

The effect of intravenous infusion of acetate, propionate and butyrate (0, 3, 10, 30 mumol kg-1 min-1 over 40 min) on the secretion of growth hormone (GH), insulin and glucagon in response to growth hormone-releasing factor (GRF) injection (0.25 micrograms/kg, 10 min after the onset of acid infusion) was determined in six sheep. The intravenous injection of GRF caused a marked increase in plasma GH at every dose of each acid. The GH response to GRF was unaffected by an intravenous infusion of acetate. The basal plasma levels of insulin, glucagon and glucose were unchanged by acetate infusion. The infusion of propionate markedly suppressed the GH response to GRF in a dose-dependent manner. Propionate produced increases in plasma insulin, glucagon and glucose concentrations. Butyrate infusion also caused a significant attenuation of GRF-induced GH secretion. Butyrate infusion stimulated the secretion of both insulin and glucagon and caused hyperglycemia. After cessation of the infusion of propionate or butyrate plasma GH tended to increase again. Plasma somatostatin concentrations, which were measured only for the highest dose of butyrate, were unchanged during acid infusion, but increased on discontinuing the infusion. It is concluded that propionate and butyrate suppress GH secretion, while stimulating the secretion of insulin and glucagon in sheep.
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PMID:Inhibitory effect of volatile fatty acids on GRF-induced GH secretion in sheep. 795 18

Cortistatin (CST) is a recently described neuropeptide with high structural homology with somatostatin. Its mRNA is restricted to gamma amino butyric acid (GABA)-containing cells in the cerebral cortex and hippocampus. CST modulates the electrophysiology of the hippocampus and cerebral cortex of rats; hence, it may be modulating mnemonic processes. In this study, we have evaluated the effect of CST and somatostatin (SS) on short- and long-term memory (STM and LTM, respectively), as well as on the extinction of the behavior by using the footshock passive avoidance behavioral test. In addition, we tested the ability of both neuropeptides to affect the generation of cAMP in hippocampal neurons in culture. Results showed that the administration of either CST or SS into the hippocampal CA1 deteriorates memory consolidation in a dose-response fashion and facilitates the extinction of the learned behavior. CST was more potent than SS. Likewise, CST increases cAMP while SS decreases it. These results strongly support a modulatory role for CST in memory processes.
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PMID:Cortistatin modulates memory processes in rats. 1070 Jun

Molecular imaging can reveal in vivo analysis and quantification of biochemical reactions. To enable cell-surface imaging of receptors, novel ligands have been developed which can be radiolabeled or imaged by bioluminescence. Specific examples include somatostatin receptors, estrogen and progesterone receptors, receptors involved in adhesion and externalization of phosphatidyl serine as an indicator of apoptosis. Central nervous system imaging can be carried out using ligands for receptors including dopamine, serotonin and Gamma amino butyric acid (GABA). In addition, tumor and metabolic imaging can be carried out with the Na-K ATPase pump using the tracer thallium-201 for SPECT or F-18 FDG for PET imaging. Finally, novel receptors or endogenous metabolic pathways can be analyzed combining cell-gene therapy to create specific tracer targets in cells that can be studied by molecular imaging. The challenge of molecular imaging is to first identify key pathways that are unique for a specific disease processes, such as atherosclerosis, cancer, CNS disorders, immunologic and arthritis disorders and next to devise a high-affinity specific small molecular ligand that can be adapted to be a radiolabeled tracer to study this pathway. Advances in genomics and proteomics combine with new peptide-chemistry approaches should provide a large number of targets and tracers in the near future to achieve these imaging objectives.
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PMID:Molecular imaging: new applications for biochemistry. 1255 16

Primary dystonia is a common movement disorder with an unknown pathophysiology, but basal ganglia dysfunctions seem to play a critical role. Previous studies in the dtsz mutant hamster, an animal model of primary paroxysmal dystonia, demonstrated a deficit of striatal gamma-amino-butyric acid (GABA) containing interneurons, which normalized at the age of the spontaneous remission of the symptoms. Whereas the reduction of striatal parvalbumin-reactive interneurons is thought to be critically involved in the pathogenesis of dystonia in the hamster mutant, the impact of a reduced density of nitric oxide synthase (NOS) reactive interneurons within the striatum is still unclear. Beside GABA, these interneurons contain somatostatin, neuropeptide Y, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and neuronal NOS, an enzyme which produces NO after the activation of the interneurons. In order to clarify if the reduced density of NOS-reactive interneurons contributes by an altered striatal production of nitric oxide (NO) to the occurrence of dystonic attacks in the hamster mutant, we performed microinjections of the NOS inhibitors 7-nitroindazole (7-NI) and Nomega-propyl-L-arginine (NPLA) and of the precursor of NO, L-arginine, into the striata of dtsz hamsters. Neither 7-NI (0.1 and 0.4 microg per hemisphere) and NPLA (2.5, 5 and 7.5 microg per hemisphere) nor L-arginine (9 and 18 microg per hemisphere) exerted any effects on the severity of dystonic movements in the dtsz mutant. Therefore, a critical involvement of striatal changes of NO in the pathophysiology of dystonic attacks in the dtsz hamster cannot be confirmed by the results of these pharmacological examinations. In view of the ontogenetic reduction of the other types of GABAergic interneurons, the deficit of NOS-reactive interneurons is possibly due to the same underlying unknown mechanism, but is less important for the pathophysiology of primary paroxysmal dystonia in the dtsz hamster mutant.
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PMID:Striatal microinjections of nitric oxide synthase inhibitors and L-arginine fail to exert effects on paroxysmal dystonia in the dtsz mutant. 1642 62

Sodium butyrate (SB) is used as an acidifier in animal feed. We hypothesized that supplemental SB impacts gastric morphology and function, depending on the period of SB provision. The effect of SB on the oxyntic and pyloric mucosa was studied in 4 groups of 8 pigs, each supplemented with SB either during the suckling period (d 4-28 of age), after weaning (d 29 to 39-40 of age) or both, or never. We assessed the number of parietal cells immunostained for H+/K+-ATPase, gastric endocrine cells immunostained for chromogranin A and somatostatin (SST) in the oxyntic mucosa, and gastrin-secreting cells in the pyloric mucosa. Gastric muscularis and mucosa thickness were measured. Expressions of the H+/K+-ATPase and SST type 2 receptor (SSTR2) genes in the oxyntic mucosa and of the gastrin gene in the pyloric mucosa were evaluated by real-time RT-PCR. SB increased the number of parietal cells per gland regardless of the period of administration (P < 0.05). SB addition after, but not before, weaning increased the number of enteroendocrine and SST-positive cells (P < 0.01) and tended to increase gastrin mRNA (P = 0.09). There was an interaction between the 2 periods of SB treatment for the expression of H/K-ATPase and SSTR2 genes (P < 0.05). Butyrate intake after weaning increased gastric mucosa thickness (P < 0.05) but not muscularis. SB used orally at a low dose affected gastric morphology and function, presumably in relationship with its action on mucosal maturation and differentiation.
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PMID:Supplemental sodium butyrate stimulates different gastric cells in weaned pigs. 1864 Nov 86

The majority of cortical interneurons use GABA (gamma amino butyric acid) as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identified by the expression of parvalbumin (PV), calretinin (CR) and somatostatin (SOM). Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important first step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin), CR + SOM, CR + NPY (neuropeptide Y), CR + VIP (vasointestinal polypeptide), SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase), CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.
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PMID:Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining. 1895 97

Nerve injury increases the spinal cord expression and/or activity of voltage- and ligand-gated ion channels, peptide receptors, and neuroimmune factors, which then drive dorsal horn neuron hyperexcitability. The intensity and duration of this central sensitization is determined by the net activity of local excitatory and inhibitory neurotransmitter systems, together with ongoing/evoked primary afferent activity and descending supraspinal control. Spinal endogenous inhibitory systems serve as opposing compensatory influences and are gaining recognition for their powerful capacity to restrain allodynia and hyperalgesia. These include numerous G protein-coupled receptors (mu- and delta-opioid, alpha(2)-adrenergic, purinergic A1, neuropeptide Y1 and Y2, cannabinoid CB1 and CB2, muscarinic M2, gamma-amino-butyric acid type B, metabotropic glutamate type II-III, somatostatin) and perhaps nuclear receptors (peroxisome proliferator-activated receptor gamma). Excessive downregulation or defective compensatory upregulation of these systems may contribute to the maintenance of neuropathic pain. An increasing number of pharmacotherapeutic strategies for neuropathic pain are emerging that mimic and enhance inhibitory neurotransmission in the dorsal horn.
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PMID:Spinal inhibitory neurotransmission in neuropathic pain. 1945 81


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