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)

Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Screening of adrenal medullary neuropeptides for putative neurotrophic effects. 163 76

In mature rat sensory neurons, expression of the gene for the growth-associated protein, GAP43, was studied by in situ hybridization with a cDNA probe. Among neurons in normal lumbar dorsal root ganglia, labeling for GAP43 mRNA was heterogeneous, approximately one-half of the neurons being densely labeled. To characterize the latter population, individual neurons were examined in adjacent sections processed either for GAP43 hybridization or NGF-receptor radioautography. Virtually all neurons with high-affinity NGF binding sites had high basal levels of GAP43 mRNA and most GAP43-positive neurons bore NGF receptors. Another NGF-responsive population, sympathetic neurons in the superior cervical ganglion, also had high basal concentrations of GAP43 mRNA. Further co-localization studies in dorsal root ganglia were performed with immunohistochemistry for somatostatin and enzyme histochemistry for acid phosphatase. The latter 2 groups of sensory neurons have been previously shown to lack high-affinity receptors and were here shown to have low basal concentrations of GAP43 mRNA. From this and earlier studies, it can be assumed that substance P-immunoreactive neurons and strongly positive CGRP neurons synthesize GAP43 at high basal rate. One week following peripheral nerve transection, almost all neurons had high concentrations of GAP43 mRNA without correlation with NGF binding. Intrathecal infusion of NGF after the sciatic nerve was cut did not strongly influence this post-traumatic elevation in GAP mRNA. In normal dorsal root ganglia, neurons that have high-affinity NGF binding sites and are therefore potentially responsive to NGF also have high basal rates of synthesis of GAP43.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between GAP43 and nerve growth factor receptors in rat sensory neurons. 215 65

Counts performed on dissociated cell cultures of E10 chick embryo dorsal root ganglia (DRG) showed after 4-6 days of culture a pronounced decline of the neuronal population in neuron-enriched cultures and a net gain in the number of ganglion cells in mixed DRG cell cultures (containing both neurons and nonneuronal cells). In the latter case, the increase in the number of neurons was found to depend on NGF and to average 119% in defined medium or 129% in horse serum-supplemented medium after 6 days of culture. The lack of [3H]thymidine incorporation into the neuronal population indicated that the newly formed ganglion cells were not generated by proliferation. On the contrary, the differentiation of postmitotic neuroblasts present in the nonneuronal cell compartment was supported by sequential microphotographs of selected fields taken every hour for 48-55 hr after 3 days of culture. Apparently nonneuronal flat dark cells exhibited morphological changes and gradually evolved into neuronal ovoid and refringent cell bodies with expanding neurites. The ultrastructural organization of these evolving cells corresponded to that of primitive or intermediate neuroblasts. The neuronal nature of these rounding up cell bodies was indeed confirmed by the progressive expression of various neuronal cell markers (150 and 200-kDa neurofilament triplets, neuron specific enolase, and D2/N-CAM). Besides a constant lack of immunoreactivity for tyrosine hydroxylase, somatostatin, parvalbumin, and calbindin-D 28K and a lack of cytoenzymatic activity for carbonic anhydrase, all the newly produced neurons expressed three main phenotypic characteristics: a small cell body, a strong immunoreactivity to MAG, and substance P. Hence, ganglion cells newly differentiated in culture would meet characteristics ascribed to small B sensory neurons and more specifically to a subpopulation of ganglion cells containing substance P-immunoreactive material.
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PMID:Differentiation of postmitotic neuroblasts into substance P-immunoreactive sensory neurons in dissociated cultures of chick dorsal root ganglion. 243 96

To begin to study the factors regulating the synthesis and release of substance P (SP) in the sensory vagus nerve, cultures of neonatal rat nodose ganglia were developed. In microexplant cultures, obtained from small fragments of nodose ganglia, SP was present in low amounts: after 3 weeks, 141 +/- 36 pg per well, 10 ganglia equivalents per well. To enhance neuron survival, nodose ganglia were enzymatically dissociated using neutral protease. Estimated survival at 5 days was 20-30%, with 800-1200 surviving neurons per plated ganglion, and decreased slowly thereafter. Specific SP immunostaining was present in 10-20% of neurons, mostly of small diameter (18-22 micron). SP content was low for 5 days then rose progressively after 14 days to 80-150 pg per plated ganglion. The addition of nerve growth factor (NGF, 100 ng/ml) to the culture medium did not alter neuron survival. However, SP content was doubled in the presence of NGF, or fell rapidly to one-half control levels following its withdrawal: e.g. following 12 days in culture with NGF 1185 +/- 176 pg/well vs NGF withdrawn day 8-12, 592 +/- 118 pg/well, mean +/- S.D., P less than 0.01. Somatostatin, present in one-sixth the amount of SP, was unaltered by NGF. In subsequent studies, plating of neurons onto previously dissociated rat atriacytes increased survival by 50% but did not alter SP content per surviving neurons. These studies demonstrate that SP is present in dissociated cultures of rat vagal sensory neurons; the quantities and estimated net synthesis rate correspond to previous observations in vivo. The studies also demonstrate that SP content but not neuron survival are regulated by NGF in nodose ganglion neurons. This model may prove valuable for the study of SP and other sensory neuropeptides in this important class of visceral afferent neurons.
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PMID:Substance P content in cultured neonatal rat vagal sensory neurons: the effect of nerve growth factor. 245 2

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

We have investigated several phenotypic features of the catecholamine-positive (CA+) cell population that develops in quail neural crest cultures. The number, spatial distribution, and morphology of CA+ and tyrosine hydroxylase-positive (TH+) cells are similar at all ages examined, suggesting that these 2 cell classes are identical. Neither CA+ nor TH+ cell bodies or processes were stained using antisera that recognize the 70 or 160 kDa subunits of chicken neurofilament protein. Other cell bodies and fibers in the cultures (which were CA- and TH-) were stained with these neurofilament antisera. The uptake and storage of 3H-norepinephrine by neural crest cultures containing CA+ cells were inhibited in the presence of desmethylimipramine and by incubation at 0 degrees C, but were unaffected by normetanephrine. Overnight treatment with reserpine eliminated histochemically detectable CA fluorescence from the cultures. Chronic reserpine treatment from day 2 to 7 in vitro prevented the appearance of CA+ cells, while normal numbers of TH+ and somatostatin-like immunoreactive (SLI) cells developed. The number and light-microscopic morphology of the CA+ cells that developed in these cultures were not dramatically altered by either exogenous NGF or 6-hydroxydopamine. Using the method of Grillo et al. (1974), we have demonstrated that the CA+ cells observed in the light microscope corresponded to cells containing abundant cytoplasmic granular vesicles (GV) characteristic of catecholamine storage granules observed in other systems. The GV diameters were quite similar in cells examined after 5, 7, 14, and 21 d in vitro. Most GV were 50-200 nm in diameter and were distributed in a unimodal manner, with the observed modal values in the range of 85-115 nm at the ages examined. The number of GV/micron2 of cytoplasmic area remained quite constant at all ages examined. These data, taken together with other available information, suggest that the CA+ cells that differentiate in our neural crest cultures resemble, in many respects, the small, intensely fluorescent cells found in autonomic ganglia and extra-adrenal chromaffin tissue of many species. At present, we do not know if the CA+ cells that differentiate in our neural crest cultures are a stable endpoint of development or whether they are a developmental intermediate in adrenergic differentiation that is normally observed only transiently during the development of avian sympathetic ganglia in vivo, but that can persist under our tissue culture conditions.
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PMID:Phenotypic properties of catecholamine-positive cells that differentiate in avian neural crest cultures. 289 Jul 25

Brain-derived neurotrophic factor (BDNF) specifically enhances and maintains the expression of neuropeptide Y (NPY) and somatostatin (SOM) in cultured neocortical neurons (Nawa et al., 1993). In this article, we examined its effects in vivo on neuropeptide expression in various brain regions by injecting BDNF into the cerebroventricle of newborn rats. Repeated administration (2x) of BDNF increased contents of NPY-like immunoreactivity (NPY-LI) and substance P (SP)-LI most markedly in the anterior neocortex by 11- and 24-fold, respectively, in comparison to values in the animals receiving control injection. A smaller but significant increase was also observed in immunoreactivity for somatostatin (SOM), enkephalin (ENK), and cholecystokinin (CCK). mRNA for NPY, SP, and SOM was similarly upregulated in the anterior neocortex, suggesting that BDNF enhances peptide synthesis rather than inhibiting peptide release or degradation. Among the brain regions examined, however, peptidergic responses to BDNF were different with respect to their spatial distribution and time course. Induction of SP-LI, NPY-LI, and SOM-LI around the injection site was most pronounced in cortical layers II/III, layers IV-VI, and layer VI, respectively. Peptidergic immunoreactivity was also enhanced in other brain regions ipsilateral to the injection site, for example, NPY-LI in the hippocampus, thalamic nuclei, and striatum, and SOM-LI in the striatum. A single injection of BDNF elevated SP-LI to a plateau level within 12 hr while NPY-LI and SOM-LI reached maximum levels at 48 hr, and then all returned to control levels at 68 hr. In contrast, the same dose of NGF had no influences on the neuropeptide levels at 48 hr. These observations suggest that BDNF regulates the development of neuropeptide expression in the CNS in a plastic manner.
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PMID:Intraventricular administration of BDNF increases neuropeptide expression in newborn rat brain. 751 53

This study was undertaken in order to establish the presence of pluripotential neuroblasts in the developing chick CNS. This has been suggested by our previous observations that expression of emerging neuronal phenotypes in the chick embryo CNS is affected by exposure to neurotrophic substances (i.e., GHRH, SRIF, NGF, EGF, muscle-derived factors) or neurotoxins such as ethanol. We have proposed that one mechanism whereby these substances elicit their effects is by shifting phenotypic expression in populations of pluripotential neuroblasts. In order to establish the presence of significant populations of pluripotential neuroblasts, cultures obtained from 3-day-old whole chick embryos (E3WE) were double-stained with antibodies to markers specific for four neuronal phenotypes in various permutations. Cultures at 6 DIV were tested for the presence of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), and somatostatin (SRIF) alone, and in various combinations. We observed a colocalization of all phenotypic markers within neuronal perikarya and processes in more than fifty percent of neuronal cells in these cultures. These data suggest that developing neuroblasts at this stage of embryogenesis possess the machinery necessary to adopt multiple neuronal phenotypes. The colocalization of neurotransmitter proteins in early neuroblasts (60 hr of embryogenesis) supports the recent concept that these substances themselves may influence phenotypic expression and also supports our idea that microenvironmental factors (i.e., ethanol, growth factors) provide signals which affect emerging phenotypes.
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PMID:Early neuroblasts are pluripotential: colocalization of neurotransmitters and neuropeptides. 756 50

Neurotrophins, which are structurally related to nerve growth factor, have been shown to promote survival of various neurons. Recently, we found a novel activity of a neurotrophin in the brain: Brain-derived neurotrophic factor (BDNF) enhances expression of various neuropeptides. The neuropeptide differentiation activity was then compared among neurotrophins both in vivo and in vitro. In cultured neocortical neurons, BDNF and neurotrophin-5 (NT-5) remarkably increased levels of neuropeptide Y and somatostatin, and neurotrophin-3 (NT-3) also increased these peptides but required higher concentrations. At elevating substance P, however, NT-3 was as potent as BDNF. In contrast, NGF had negligible or no effect. Neurotrophins administered into neonatal brain exhibited slightly different potencies for increasing these neuropeptides: The most marked increase in neuropeptide Y levels was obtained in the neocortex by NT-5, whereas in the striatum and hippocampus by BDNF, although all three neurotrophins increased somatostatin similarly in all the brain regions examined. Overall spatial patterns of the neuropeptide induction were similar among the neurotrophins. Neurons in adult rat brain can also react with the neurotrophins and alter neuropeptide expression in a slightly different fashion. Excitatory neuronal activity and hormones are known to change expression of neurotrophins. Therefore, neurotrophins, neuronal activity, and hormones influence each other and all regulate neurotransmitter/peptide expression in developing and mature brain. Physiological implication of the neurotransmitter/peptide differentiation activities is also discussed.
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PMID:Regulation of neuropeptide expression in the brain by neurotrophins. Potential role in vivo. 757 4

The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d-tubocurarine. The most heavily labeled cells are GABA-containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input.
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PMID:Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression. 847 87


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