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)

Inhibition of the phosphorylation of the synaptic plasma membrane (SPM) protein B50 by [D-Trp8]-somatostatin in vitro is time-dependent. Increasing the time of incubation of hippocampal synaptic plasma membranes with the peptide from 15 sec to 30 min prior to addition of 7.5 microM [gamma-32P]ATP results in a complete reduction of B50 phosphorylation. Incubation of synaptic plasma membranes for 30 min in the absence of peptide does not alter basal B50 phosphorylation. Neither ACTH nor beta-endorphin produces similar effects--inhibition of B50 phosphorylation by ACTH is maximal at 15 sec and beta-endorphin produces only a small inhibition, even after 30 min. [D-Trp8]-somatostatin is not activating a membrane-bound protease, since maximal inhibition of B50 phosphorylation by the peptide is seen in the presence of leupeptin or bacitracin. Hippocampal synaptic plasma membranes contain protein phosphatase activity. Assays of B50 phosphorylation in synaptic plasma membranes done under conditions that favor either net phosphorylation or dephosphorylation are consistent with inhibition of protein phosphatase activity by [D-Trp8]-somatostatin. This evidence suggests that [D-Trp8]-somatostatin interacts with SPM binding sites in the hippocampus, which may alter the activity of an endogenous protein phosphatase to determine the degree of B50 phosphorylation.
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PMID:Characteristics of [D-Trp8]-somatostatin-sensitive B50 phosphorylation. 287 46

Our laboratory has reported previously the characteristics of specific AVP binding to rat hippocampal synaptic membranes (SPM) in the presence of Ni2+ [Costantini MG, Pearlmutter AF: J Biol Chem 259: 11739-11745, 1984]. We extended our investigation to determine the effects of Ni2+, (AVP), and AVP analogs on SPM protein phosphorylation. Ni2+ (5 mM) caused a dramatic reduction in phosphorylation of most SPM phosphoproteins. The most prominent protein which is phosphorylated in SPM has a molecular weight of 48 kilodaltons (KDa) and has been named B50 or F1; this protein shows altered phosphorylation in vitro in response to long-term potentiation in vivo as well as changes induced by exposure of SPM to ACTH (1-24), dopamine, and somatostatin. AVP and related peptides reduced phosphorylation of this pre-synaptic phosphoprotein in the following order of potency: AVP = oxytocin greater than DG-AVP greater than dDAVP greater than d(CH2)5Tyr(Me)AVP = [pGlu4,Cyt6]AVP-(4-9). Except for the pressor antagonist d(CH2)5Tyr(Me)AVP, this corresponds to their relative efficacy in displacing 3H-AVP from high-affinity specific binding sites on rat hippocampal synaptic membranes. Ni2+ did not alter the degree of inhibition caused by the peptides. When SPM were treated with AVP after the attainment of maximum 32P incorporation, AVP inhibited dephosphorylation over a 30-min period. Our results show that AVP can alter both phosphorylation and dephosphorylation of hippocampal SPM phosphoproteins in vitro; the direction of these effects depends upon experimental conditions. Since B50/F1 is known to be a substrate for protein kinase C, AVP may act by inhibition of protein kinase C activity, either directly or indirectly.
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PMID:Effects of arginine vasopressin on protein phosphorylation in rat hippocampal synaptic membranes. 303 58

The distributions of peptide-immunoreactive nerve fibres and cell bodies in lumbosacral paravertebral sympathetic ganglia of young cats were analysed with antibodies to calcitonin gene-related peptide, enkephalin, neurotensin, somatostatin, substance P, galanin, neuropeptide Y and vasoactive intestinal polypeptide. Fairly dense networks of nerve fibres showing enkephalin-, neurotensin-, somatostatin- or substance P-like immunoreactivity were observed in the ganglia. Double-staining experiments revealed that enkephalin- and somatostatin-immunoreactive nerve fibres preferentially surrounded calcitonin gene-related peptide- and/or vasoactive intestinal polypeptide-immunoreactive cell bodies. Neurotensin- and substance P-immunoreactive nerve fibres were mainly associated with neurons showing neuropeptide Y and/or galanin-like immunoreactivity. Occasional nerves containing calcitonin gene-related peptide-, galanin-, neuropeptide Y- or vasoactive intestinal polypeptide-like immunoreactivity were observed. These fibres did not seem to have any direct regional distribution within the ganglia. In kittens surviving for three months after early postnatal sciatic nerve resection, no calcitonin gene-related peptide-immunoreactive cell bodies could be detected in ganglia ipsilateral to the operation. In contrast, vasoactive intestinal polypeptide-like immunoreactivity, which partly co-exists with calcitonin gene-related peptide, was observed to the same extent as in control ganglia. Furthermore, almost all of the somatostatin-immunoreactive varicose nerve fibres had disappeared, whereas a fairly dense network of calcitonin gene-related peptide-immunoreactive nerve fibres could be observed. This change was paralleled by an increased content of nerve fibres that were immunoreactive to antibodies against the growth-associated protein GAP-43 (also known as B-50). The present findings suggest that experimental perturbations where postganglionic neurons are separated from their target areas by axotomy, not only induce differential changes in neurotransmitter expression in the principal ganglion cells, but also in preganglionic sympathetic neurons projecting to the ganglia. One possible explanation for the occurrence of an axotomy-induced network of calcitonin gene-related peptide-immunoreactive nerve fibres, is that extrinsic sensory nerve fibres grow into the ganglia after the sciatic nerve lesion. Thus, these findings seem to suggest one additional possibility with regard to the question of a possible interaction between sympathetic and sensory neurons after peripheral nerve injury.
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PMID:Peptide-immunoreactive neurons and nerve fibres in lumbosacral sympathetic ganglia: selective elimination of a pathway-specific expression of immunoreactivities following sciatic nerve resection in kittens. 769 Sep 13

Lesions of the nucleus basalis of Meynert (NBM) have been used to mimic, in part, cholinergic deficits occurring in age-related neurodegenerative disorders, i.e., Alzheimer's disease. In our study, the effect of a persistent cholinergic denervation of the fronto-parietal cortex on neuropeptide Y (NPY) and somatostatin (SOM) was examined in young adult (3 months old) and aging (> 18 months old) rats, 1, 3 and 6 months after bilateral stereotaxic NBM lesions with quisqualic acid. In aging, non-lesioned rats a significant decrease in radioimmunologically and immunohistochemically detectable NPY and SOM was found with no further changes after lesions. Morphological markers for these peptidergic populations (cell size and number, NADPH-diaphorase histochemistry, electron microscopy) demonstrated no signs of alterations in both age groups after lesion. Densitometric analysis of peptide fibre networks displayed a heterogeneous response with a significant rarefication in young rats 1 month after the lesion, followed by restoration and a tendency towards increase 6 months post lesioning in individual animals. These findings were confirmed by radioimmunological measurements. Examination of synaptic and cytoskeletal markers, i.e., synaptophysin, GAP-43, MAP-2, Tau-1 and amyloid precursor protein, did not reveal any signs for neuronal reorganization or sprouting. These data are discussed in the context of plasticity and pathology in age-related neurodegenerative disorders with cholinergic impairment.
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PMID:Neuropeptide Y and somatostatin in the neocortex of young and aging rats: response to nucleus basalis lesions. 780 68

The physiological characteristics and significance of long-term potentiation in the hippocampus were summarized. In particular, it was pointed out that different mechanisms are involved in the production of hippocampal LTP between the mossy fiber-CA3 system and other systems such as Schaffer collateral-CA1, fimbrial fiber-CA3 and commissural/associational fiber-CA3. Furthermore, the epsilon-subspecies of protein kinase C (PKC) was demonstrated to be exclusively located at the presynaptic terminals in the hippocampus and activated by arachidonic acid, and this enzyme is suggested to be involved in the production of LTP through a phosphorylation of GAP-43, while the gamma-subspecies of PKC may be postsynaptically involved in LTP through an activation of NMDAR1. The production of LTP in the hippocampus is facilitated by many factors such as epidermal growth factor, fibroblast growth factors, somatostatin, M1 receptor agonists and many drugs like anirasetam, bifemelane, idebenone, indeloxazine and vinpocetine, but inhibited by M2-receptor agonists, scopolamine and midazolam. In addition to electrophysiological methods, LTP-like phenomena in 2-deoxyglucose uptake and leucine incorporation can be detected. These LTP phenomena in several animal models will be useful as indices for evaluating facilitatory actions of various compounds on learning/memory functions.
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PMID:[Pharmacology of long-term potentiation]. 810 51

Botulinum toxin is widely used for the treatment of focal movement disorders, where chemodenervation is used to decrease hyperactivity in selected muscles. Beside a focal paresis, widespread effects on neuromuscular synaptic function have been demonstrated. However, reactions of motoneurons after neuromuscular chemodenervation without gross morphological lesions are largely unknown. Peripheral axotomy, in contrast, leads to profound changes in the expression of several genes, including those encoding neurotransmitters, in motoneurons. We therefore examined the expression of neurotransmitter genes in rat motoneurons six days after intramuscular botulinum toxin application in the right gastrocnemius muscle. Similar doses of botulinum toxin as used in human where injected. A focal bilateral increase in expression of the choline acetyltransferase gene and a widespread bilateral increase of the beta-calcitonin-gene-related peptide and the enkephalin genes was measured in motoneurons after botulinum toxin injection. Cholecystokinin had a lower expression after botulinum toxin injections. Growth-associated protein 43, nitric oxide synthase, somatostatin and proopiomelanocortin messenger RNA were not found in motoneurons of both groups. Our results demonstrate that changes in the expression of neurotransmitter genes in motoneurons also occur after chemodenervation but with different patterns to those found after mechanical nerve lesioning. These changes reflect focal and widespread modulative events. The knowledge of these events should lead to a better understanding of the focal paralysis and of the more widespread effects found in human after intramuscular injection of botulinum toxin.
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PMID:Expression of neurotransmitter genes in rat spinal motoneurons after chemodenervation with botulinum toxin. 914 3

The aim of this study was to compare immunoreactivities for substance P with other enteric neuropeptides and GAP-43, a general marker for enteric nerves, in normal human colon and in different stages of ulcerative colitis. Tissue samples from normal colon and regions of ulcerative colitis colon were obtained at surgery and immunostained for substance P, vasoactive intestinal polypeptide (VIP), somatostatin, calcitonin gene-related peptide (CGRP), enkephalin, galanin, GAP-43, and neuron-specific enolase (NSE). Visual examination and semiquantitative analysis revealed a clear increase in the immunoreactivity for substance P in ulcerative colitis, whereas no differences were observed in the distribution of the other peptides. Therefore, quantitative analysis was performed only for substance P immunoreactivity in the lamina propria, circular muscle layer, and myenteric ganglia. In the lamina propria, the score of total intensity of substance P immunoreactivity was 0.55 +/- 0.15 (mean +/- SEM) in normal colon, 1.30 +/- 0.35 (p = 0.087) in least affected colon, and 2.22 +/- 0.28 (p < 0.001) in moderately affected colon, whereas no significant differences were observed in immunoreactivities for GAP-43. Similar results were obtained for the mean substance P- or GAP-43-immunoreactive area. In the circular muscle layer, the number, density, total intensity, and perimeter of substance P- and GAP-43-immunoreactive fibers were essentially similar in normal colon, and in mild or moderately affected colon. We conclude that ulcerative colitis does not change the density of gut innervation as a whole. However, the density of substance P-containing nerves is specifically increased, probably due to increased peptide synthesis leading to better visibility of the fibers.
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PMID:Quantitative comparison of growth-associated protein-43 and substance P in ulcerative colitis. 1137 21

Targeting of dorsal root ganglia by diabetes could account for the selective sensory abnormalities that patients with early diabetic polyneuropathy develop. In this work, we addressed survival, phenotype and gene expression in sensory neurones in lumbar dorsal root ganglia in a long-term model of experimental streptozotocin-induced diabetes in rats, designed to reflect human disease. Motor and sensory conduction slowing developed early, by the 2-month time point. At 2 months, sensory neurones had no detectable alterations in their calibre or gene expression, assessed using quantitative in situ hybridization studies for mRNA markers that included alpha CGRP, beta CGRP, NFM, t alpha 1-tubulin, SP, VIP, B50 (GAP43), galanin, somatostatin, PACAP, HSP27, c-jun, SNAP 25, p75, TrkA, TrkB and TrkC. By 12 months, however, diabetics had developed neurone perikaryal and distal axon atrophy, accompanied by generalized downregulation of mRNA expression, particularly of CGRP transcripts, PACAP, SP, NFM, p75, trkA and trkC. With the exception of HSP-27, no elevation in mRNAs that increase after injury, such as VIP, galanin, CCK, PACAP, B50 and t alpha 1-tubulin, was observed and constitutive levels, when detectable, trended towards lower rather than increased levels. There was relative preservation of neurone numbers at 12 months; only a non-significant trend towards fewer diabetic neurones was detected using a rigorous and systematic physical dissector counting approach through the entire L5 ganglia. There was no change in the relative populations of CGRP- and SP-immunoreactive neurones. Our findings indicate that even long-term experimental diabetes is associated with relative preservation of sensory neurone populations, but the neurones are atrophic and their gene expression is altered. This pattern of change differs from that following axotomy, implies a degenerative rather than an injury phenotype and has important implications for how such neurones might be rescued.
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PMID:Does diabetes target ganglion neurones? Progressive sensory neurone involvement in long-term experimental diabetes. 1167 32

The central nervous system (CNS) of primates, including humans, is more complex than the CNS of other mammals. In particular, the cerebral cortex expands during evolution and this has resulted in the emergence of higher cognitive abilities in primates. Recent neurochemical and neuroanatomical methods have clarified the presence of various neuroactive substances including neuropeptides, neurotrophic factors and growth associated proteins in the developing mammalian cerebral cortex. Among these signal molecules, we have focused on somatostatin (SRIF), neurotrophins (BDNF, NT-4/5 and NT-3) and their receptors (Trk), growth associated proteins such as GAP-43 and SCG-10 during the development and aging of primate CNS. We found that although full-length TrkB, a high affinity receptor for BDNF and NT4/5, was detected from the embryonic stage to adulthood, the level of truncated TrkB which lacks tyrosine kinase domain, only increased after birth. This development of truncated TrkB correlated well with down-regulation in the gene expression of GAP-43 and SCG-10. The reductions of GAP-43 and SCG-10 may result in the elimination of callosal axons in the monkey cerebral cortex after birth. The highest levels of BDNF protein in the various cerebral cortices occurred between postnatal 1 and 6 when the number of synapses is highest. In contrast, there was no transient increase in the levels of NT4/5 or NT3 after birth. These findings suggest that BDNF is one of the candidates for the synaptic development of the primate cerebral cortex. During aging processes, we observed decreases in the levels of SRIF and BDNF mRNAs in the cerebral cortex. Since BDNF is an upstream gene expression molecule of SRIF, the decline of SRIF mRNA during aging may be due to the decrease in the gene expression of BDNF. Similar reductions of gene expressions of SRIF and BDNF in the brains of the patients with Alzheimer's disease, suggest that aged monkeys are good model animals for these neuro-degenerative diseases.
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PMID:[Molecular mechanisms for the development and aging of the primate central nervous system]. 1548 19

Altered inhibition-excitation balance is implicated in brain aging. We hypothesized that expression of 14 genes encoding proteins localized to synapses or interneurons would show age-related changes relative to 1 another in postmortem tissue from the prefrontal cortex of 37 individuals (18-78 years) and that synaptic or interneuron markers would be differentially correlated with human brain volumes across aging. The majority of genes examined were differentially expressed with age, most being downregulated. Expression of 3 interneuron-related genes was significantly negatively associated with age (calbindin, somatostatin, cholecystokinin), whereas 3 synapse-related genes showed significant age-related expression change (PSD95, GAP43, VGLUT1). On covarying for 2 glial markers (GFAP, IBA1), all 3 interneuron genes and 1 synaptic gene (Growth-associated protein 43) remained significant. Two genes were significantly associated with total brain volume (calbindin, complexin 2) and a marker of synaptic density (synaptophysin) was significantly associated with cortical gray matter volume. Age-related change in expression of genes involved in maintenance of inhibition-excitation balance and regulation of prefrontocortical network dynamics suggests these pathways may contribute to brain aging.
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PMID:Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex. 3003 Dec 32


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