Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Manipulation of neurotrophic support is a developing strategy for new therapy aimed at neurodegenerative diseases. This study demonstrates reduced content and retrograde transport of endogenous nerve growth factor (NGF) in sciatic nerve of diabetic rats. There were also reductions in the diabetic rats in NGF protein and mRNA in skin and muscle of the hindlimb. These deficits correlated with reductions in substance P and calcitonin gene-related peptide--both products of NGF-influenced genes in primary afferents. These manifestations of deficient neurotrophic support were corrected by intensive insulin treatment and surmounted by administration of exogenous human recombinant NGF in a dose-related manner. Impaired neurotrophic support may, therefore, participate in the pathogenesis of diabetic and other peripheral neuropathies.
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PMID:Human recombinant nerve growth factor replaces deficient neurotrophic support in the diabetic rat. 761 16

Disruption of dopaminergic neurotransmission in the striatum by neurotoxic lesions of the substantia nigra leads to increases in glutamic acid decarboxylase and proenkephalin messenger RNA expression, and to decreases in preprotackykinin (the precursor molecule for substance P) messenger RNA expression in the two populations of striatal medium-sized spiny projection neurons. These cells also express TrkB, the neurotrophin receptor for brain-derived neurotrophic factor and neurotrophin 4/5, and TrkC, the receptor for neurotrophin-3. Since there is some indication that exogenous brain-derived neurotrophic factor can exert neuromodulatory effects in the basal ganglia, we studied the effects of repeated intrastriatal injections of the four members of the neurotrophin family of neural growth factors, nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 on the expression of striatal neurotransmitter-related genes in the unilaterally 6-hydroxydopamine-lesioned rat using in situ hybridization histochemistry. We found that 4 micrograms/day of brain-derived neurotrophic factor or neurotrophin-4/5 when injected intrastriatally for eight consecutive days led to a normalization of the denervation-induced decrease of preprotachykinin messenger RNA when compared to animals injected with equivalent doses of nerve growth factor, neurotrophin-3, or vehicle. Neurotrophin-4/5 alone also normalized expression of messenger RNA encoding the 67 x 10(3) mol. wt isoform of glutamate decarboxylase, while none of the neurotrophins had a significant effect on preproenkephalin messenger RNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum. 761 69

Three E box motifs, which are upstream of the major transcriptional start site, have previously been characterised in the rat preprotachykinin-A (rPPT) promoter. Only one of these, in the proximal promoter spanning nucleotides -67 to -47, has been demonstrated to support reporter gene expression in clonal cell lines under basal growth conditions. Here we demonstrate that the reporter gene expression can be further induced by the action of phorbol 12-myristate 13-acetate (TPA) and nerve growth factor (NGF), respectively, in both HeLa and the neuronally derived PC12 cells. This response is due to the E box motif and not an overlapping consensus sequence for a putative AP1 element, a class of element previously demonstrated to respond to both TPA and NGF in these cell lines. Finally, we demonstrate that this E box motif can support similar levels of reporter gene expression in primary cultures of dorsal root ganglion neurons as observed in clonal cell lines, demonstrating that E box binding complexes can (1) function as a transcriptional regulator in dorsal root ganglion neurons and (2) bind to and therefore presumably regulate rPPT promoter activity.
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PMID:Characterisation of a functional E box motif in the proximal rat preprotachykinin-A promoter. 764 42

Peripheral inflammation induced in adult rats by an intraplantar injection of complete Freund's adjuvant results in a rapid (6 h) increase in the expression of the messenger RNAs for the neuronal growth-associated protein 43 and for preprotachykinin A, the precursor for substance P, in dorsal root ganglion sensory neurons innervating the inflamed area. This increase peaks at 48 h and then declines by five days. The changes are present in the dorsal root ganglion cells innervating the inflamed skin (lumbar 4 or 5) but no elevation was found in the third lumbar dorsal root ganglion which innervates neighbouring non-inflamed skin. The increased growth-associated protein 43 messenger RNA in the dorsal root ganglion is followed by a marked increase in growth-associated protein 43-like immunoreactive fibres in the epidermis of the inflamed skin. Systemic administration of neutralizing anti-nerve growth factor antibodies immediately prior to the inflammation prevents the increase in growth-associated protein 43 and preprotachykinin A messenger RNAs in the sensory neurons. A subcutaneous injection of nerve growth factor (200 ng) into the hindpaw elevates preprotachykinin A but not growth-associated protein 43 messenger RNA in the fourth lumbar dorsal root ganglion 48 h post-injection and this could be prevented by co-administration of the anti-nerve growth factor serum. The production of nerve growth factor in inflamed target tissues leads to alterations in the phenotype of responsive adult primary sensory neurons which include a change in the levels of a growth-related protein and a peptide neuromodulator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nerve growth factor contributes to the up-regulation of growth-associated protein 43 and preprotachykinin A messenger RNAs in primary sensory neurons following peripheral inflammation. 767 1

Intraperitoneal administration of 4-methylcatechol, which is one of the potent stimulators of nerve growth factor (NGF) synthesis in vitro, induced an increase in NGF protein and NGF mRNA in the adult rat heart and submaxillary gland. The increase in NGF protein was successively translocated from the sciatic nerve to sensory or sympathetic ganglia. Repetitive administration of 1,2-diacetoxypropylbenzene, an acetylated form of 4-methylcatechol analog, caused significant elevations of substance P levels in sensory ganglia and tyrosine hydroxylase activity in superior cervical ganglia of infant rats. These observations suggest that both compounds could stimulate NGF synthesis in vivo and that the induced NGF had physiological effects on peripheral neurons.
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PMID:Pharmacological induction of physiologically active nerve growth factor in rat peripheral nervous system. 767 47

Rat chromaffin cells display phenotypic plasticity postnatally. In the presence of glucocorticoids, they retain a chromaffin cell phenotype, whilst in the presence of nerve growth factor and the absence of glucocorticoids they adopt a sympathetic neuronal phenotype. The tachykinins have some of the characteristics of a neurotrophic factor and are present in the form of a substance P afferent input in the rat adrenal medulla. We investigated the effects of stable NK1 and NK2 tachykinin receptor agonists, Ava[L-Pro,N-Me-Leu-10]SP7-11 (GR73632) and [Lys-3,Gly-8,R-Lac-Leu-9]NKA3-10 (GR64349), respectively, on the survival and phenotype of P5-7 rat chromaffin cells in vitro. GR73632 promoted neurite outgrowth, characteristic of the sympathetic neuronal phenotype, in the absence of NGF and glucocorticoids, but was without effect on survival after 2 weeks in culture. GR64349 was without effect.
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PMID:A selective tachykinin receptor agonist promotes differentiation but not survival of rat chromaffin cells in vitro. 768 Oct 11

The regulatory effects of nerve growth factor (NGF) on tachykinin biosynthesis in rat primary sensory neurons during the period of postnatal development were examined under in vivo and in vitro conditions. Administration of NGF to neonatal rats led to a significant increase in protein levels of substance P (SP) and neurokinin A (NKA) in trigeminal and dorsal root ganglia (DRG). In addition, Northern blot analysis revealed that preprotachykinin mRNA was upregulated in sensory ganglia of neonatal animals after treatment with NGF. Using a well-defined in vitro system for neonatal rat DRG and trigeminal ganglia neurons, we found that addition of NGF induced SP and NKA protein levels in a dose-dependent manner. Furthermore, preprotachykinin mRNA was markedly increased in cultured DRG and trigeminal ganglia neurons in the presence of NGF. Thus, our results clearly demonstrate that NGF regulates tachykinin gene expression and biosynthesis both in vivo and in vitro during the developmental period of rat sensory neurons.
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PMID:Nerve growth factor (NGF) regulates tachykinin gene expression and biosynthesis in rat sensory neurons during early postnatal development. 768 76

This study was designed to explore effects of experimental diabetes mellitus on expression of substance P in the trigeminal ganglion and of nerve growth factor (NGF) in the iris. Rats with streptozotocin-diabetes showed an increase in NGF mRNA in the iris (P < 0.01) which was corrected by insulin treatment. There was also an increase in the levels of mRNA for the substance P precursor, preprotachykinin (PPT), in the trigeminal ganglion of these animals, despite there being no change in GAP-43 mRNA. Since expression of both of these peptides is sensitive to NGF in vitro, we examined the effect of treatment of diabetic rats with NGF at three different doses (0.2, 0.5 and 1.0 mg/kg body weight). There was a dose-dependent increase in both gamma-PPT and GAP-43 mRNA in the trigeminal ganglia of NGF-treated diabetic rats. The findings indicate that increased NGF may be responsible for raised substance P levels in the iris.
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PMID:Changes in nerve growth factor and preprotachykinin messenger RNA levels in the iris and trigeminal ganglion in diabetic rats; effects of treatment with insulin or nerve growth factor. 776 88

We demonstrate in PC12 cells that although nerve growth factor, forskolin or potassium-evoked depolarisation independently induced minimal or no expression from the rat preprotachykinin-A gene (rPPT) promoter linked to a reporter gene, exposure of the cells to various combinations of these stimuli specifically activated the rPPT promoter in transient transfection assays.
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PMID:The rat preprotachykinin-A promoter is regulated in PC12 cells by the synergistic action of multiple stimuli. 789 49

The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states.
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PMID:Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF. 798 76


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