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)

A gate control exists by which peripheral afferents and descending pathways can modulate sensory transmission. Evidence is presented that the mechanism may exist in the substantia gelatinosa laminae II and III. This area receives all known types of peripheral afferent from skin, from viscera and from high-threshold muscle afferents. The chemistry of the region is unique. Peripheral afferent terminals contain substance P, somatostatin, and fluoride-resistant acid phosphatase. Cells in the region contain enkephalin and GABA. At least three descending systems from the brainstem terminate in the area. The anatomical substrate exists by which cells in laminae II and III can receive afferents and descending axons and intrude onto cells of laminae I, IV, and V. Stimuli limited to the axons of laminae II and III cells in the Lissauer tract produce dorsal root potential and change the excitability of mono- and polysynaptic reflexes. They also change the excitability and receptive fields of cells in laminae IV and V. Recording from single units in laminae II and III reveals cells with many unusual properties not seen in the large dorsal horn cells. These unusual properties include small receptive fields, very prolonged responses to single stimuli, prolonged habituation, and shifting receptive fields. The action of the gate control shows it to be subtle and far beyond a simple control of overall excitability. Excitations and inhibitions are independently controlled. Different types of convergent afferent may be turned on and off. There are signs of both short-and long-lasting actions. It seems that a good case has been made for the cells of substantia gelatinosa taking part in the gate control mechanism.
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PMID:The role of substantia gelatinosa as a gate control. 624 35

Rat sciatic nerves were treated with tetrodotoxin (TTX) for 4--10 days, by implanting a glass capillary tube filled with TTX into the nerve through the epineurium. Following this treatment the somatotopic organization of receptive fields in the L4 dorsal horn, an area of cord normally responding only to foot stimulation. The map was normal in animals treated with TTX. Dorsal horn levels of fluoride-resistant acid phosphatase, substance P, somatostatin, cholecystokinin-like peptide, neurotensin and neurophysin were also normal as assessed from density of staining. These results are discussed in the light of the positive changes that are seen following chronic sciatic nerve section.
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PMID:Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat. 628 71

The importance of nerve growth factor (NGF) for the development of sensory ganglia was investigated by injecting rat fetuses (16.50 days of gestation) with a single dose of anti-NGF antiserum. Four months later the treated animals showed a very large decrease in substance P- and somatostatin-like immunoreactivities in dorsal root ganglia and skin with a lesser decrease in trigeminal ganglia. Fluoride-resistant acid phosphatase, substance P-, and somatostatin-like immunoreactivities were greatly decreased in the dorsal horn of the spinal cord. No change in neurotensin- and [Met]enkephalin-like immunoreactivities was observed. The anti-NGF antiserum treatment produced a greater than 90% decrease in the number of unmyelinated dorsal root fibers and a 35% decrease in the total number of myelinated fibers. The loss in myelinated fibers was restricted to small-diameter fibers with no change in large-diameter fibers. No change in taste bud morphology was noted, thereby refuting the proposal that anti-NGF antiserum treatment may represent an animal model for familial dysautonomia. The present results indicate that NGF is a necessary requirement for the normal development of a significant population of prenatal rat dorsal root ganglion cells.
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PMID:Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia. 660 28

The isolectin B4 from Griffonia simplicifolia I binds to a subpopulation of rat small-diameter dorsal root ganglion neurons, and to fibres and presumed terminals in laminae I-II of the spinal cord dorsal horn. In the present study we investigated B4 and B4 conjugated to horseradish peroxidase as potential transganglionic tracers of somatic primary afferent neurons after injection into a peripheral nerve. We also tried to identify the specific subpopulation of dorsal root ganglion neurons that bind and ganglion neurons that bind and transport B4. Following injection of B4 or B4-horseradish peroxidase into the sciatic nerve, labelled presumed terminals that reached peak labelling at two days were found exclusively in regions of the spinal cord gray matter known to receive unmyelinated primary afferent fibres. Almost all dorsal root ganglion cells that transported B4-horseradish peroxidase also bound B4. Cell counts showed that 51% of the dorsal root ganglion neurons were B4-positive and cell area measurements that these were all in the small size range. An extensive overlap was found between B4 and fluoride-resistant acid phosphatase (85%), and between B4 and calcitonin gene-related peptide (59%). Seventeen per cent of the B4-positive cells were substance P-immunoreactive and 9% were immunoreactive to somatostatin. Minimal overlap was seen between B4-positive cells and cells positive for RT97 (3%), a selective marker of primary afferent neurons with myelinated axons. All somatostatin-immunoreactive cells and almost all (95%) of the fluoride-resistant acid phosphatase-positive cells were contained within the B4-positive population. This comprised also 58% of the cells immunoreactive to calcitonin gene-related peptide and 42% of those immunoreactive to substance P. The results obtained show that B4 binds to a subpopulation of unmyelinated primary afferent neurons, and that B4 and B4-horseradish peroxidase can be used as selective transganglionic tracers of this specific cell subpopulation.
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PMID:Transganglionic transport and binding of the isolectin B4 from Griffonia simplicifolia I in rat primary sensory neurons. 753 Mar 47

To study the appearance of polymorphic, dense multivesicular body-like structures (MBLS) occurring in the D-cells of pancreatic islets following abdominal vagotomy in the chicken, the D-cells were evaluated by means of quantitative electron microscopy, identified by immunogold labeling and characterized by a method of enzyme cytochemistry. Following vagotomy, secretory granules of the pancreatic D-cells decreased significantly in number, whereas MBLS increased significantly in number. the mean area of the cell, nucleus and mitochondria displayed no significant changes. MBLS were rarely labeled for somatostatin when subjected to immunogold staining. MBLS arranging along the Golgi stacks may possibly be formed in the Golgi apparatus. consequently, it seems unlikely that MBLS are secondary lysosomes revealing crinophagy. Some MBLS showed acid phosphatase (AcPase) activity, although the direct fusion of primary lysosomes exhibiting AcPase activity with MBLS was seldom observed. As a result, it is possible that MBLS may be a kind of modified form of secretory granules and that they may be destroyed by lysosomes under the storing condition, judging from the AcPase reaction.
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PMID:Immuno- and enzyme-cytochemical studies on the pancreatic D-cells in the chicken following vagotomy. 863 Apr 39

Expression of fusion proteins between prepro-alpha-factor and somatostatin (SRIF) in yeast, resulted in the correct processing and secretion of the heterologous 14-amino acid SRIF peptide (1). When the chimeric genes were placed under the control of yeast acid phosphatase (PHO5) promoter, significant amount of an unglycosylated form of the fusion precursor molecule accumulated intracellularly, suggesting disruption of an endoplasmic reticulum-mediated function. We report here that the appearance of the precursor is due to an alteration in the three amino terminal residues of the chimera, i.e., Met-Arg-Phe in native prepro-alpha-factor is changed to Met-Phe-Lys in the hybrids. The unglycosylated precursor represents a population of molecules that are disrupted at an early stage of targeting to or translocation across the endoplasmic reticulum membrane. Our data demonstrate that the N-terminus plays an important role in topogenesis. Furthermore, these results show that translocation and glycosylation can be uncoupled from protein synthesis in vivo, and therefore can be posttranslational events in yeast.
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PMID:Topogenic effect of positively charged N-terminal amino acid in ER translocation of yeast alpha-factor precursor. 885 54

In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.
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PMID:Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder. 972 57

Neurotomy is widely used as a model of chronic, intractable pain, the proverbial "crux medicorum". Immunohistochemical aspects of this chronic pain model are discussed in this paper, with the aim of shedding new light on the pathomechanism and possible therapeutical consequences. Central terminals of nociceptive neurons contain substance P, somatostatin and calcitonin generelated peptide or exhibit fluoride resistant acid phosphatase and thiamine monophosphatase enzyme reaction in the superficial dorsal horn of the spinal cord and in analogous structures of the brain stem. These neuropeptides and neuroproteins are expressed by the related dorsal root ganglion cells and transported via orthograde axoplasmic transport via dorsal roots to the central nervous system. Transection of the ipsilateral, segmentally related peripheral sensory nerve results in transganglionic degenerative atrophy of central terminals of primary nociceptive neurons. Transganglionic degenerative atrophy is characterized by marked ultrastructural alterations superficially similar to, but essentially differing from the signs of Wallerian degeneration which ensue after dorsal rhizotomy. Transganglionic degenerative atrophy is accompanied by depletion of marker neuropeptides and enzymes, and later by the expression of vicarious neuropeptides such as vasoactive intestinal polypeptide, neuropeptide Y and galanin and of the enzyme choline acetyl transferase. Consequences of blockade of retrograde axoplasmic transport of the nerve growth factor elicited either by perineural application of microtubule inhibitors or by perineural administration of anti-nerve growth factor are similar to peripheral neurotomy. According to recent studies described in this paper, the blockade of nerve growth factor supply to primary nociceptive neurons induces activation of c-jun in nuclei of primary nociceptive neurons probably responsible for the plasticity of the neuropeptide and neuroprotein synthesizing machinery. In contrast, invasion of and formation of pericellular baskets by noradrenergic axons can be elicited only by axotomy and not by blockade of retrograde axoplasmic transport. Involvement of nerve growth factor and the nerve growth factor-dependent immediate early genes in neuroplasticity of neuropeptidergic primary sensory neurons raise the possibility of a gene therapy of chronic intractable pain.
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PMID:Molecular plasticity of primary nociceptive neurons: relations of the NGF-c-jun system to neurotomy and chronic pain. 1292 68


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