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)

Effects of immune cytokines on neuronal gene expression have recently been examined in cultured superior cervical (sympathetic) ganglia, a widely used model system for the study of neurotransmitter plasticity. Following deafferentation and explantation into culture, interleukin-1 causes an up-regulation of the neuropeptide substance P as well as of choline acetyltransferase. Tumor necrosis factor-alpha has a similar, though less potent, action. Since interleukin-1 was ineffective in raising the concentration of substance P in pure neuronal cultures, the existence of a non-neuronally derived intermediate was postulated and found to exist in interleukin-1-conditioned medium. Antibody neutralization of either nerve growth factor or ciliary neurotrophic factor failed to affect the ability of interleukin-1 to induce substance P. Inhibition of prostaglandin biosynthesis was equally ineffective. However, immunoprecipitation of leukemia inhibitory factor from interleukin-1-conditioned medium eliminated substance-P-inducing activity, suggesting leukemia inhibitory factor as a possible interleukin-1-induced intermediate. The ability of interleukin-1 to induce leukemia inhibitory factor mRNA strengthens this conclusion. Glucocorticoid hormones block the interleukin-1 induction of leukemia inhibitory factor, which explains why they block the interleukin-1 induction of substance P.
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PMID:Neural-immune interactions in sympathetic ganglia. 752 15

The spinal pia mater receives a rich innervation of small sensory axons via the ventral roots. Other sensory axons enter the ventral roots but end blindly or turn abruptly in hairpin loop-like formations and continue in a distal direction. In the present study, the content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, growth-associated protein (GAP-43)-, and low-affinity neurotrophin receptor protein (p75NGFr)-like immunoreactivity (-LI) associated with these different types of sensory axons was assessed with light and electron microscopic immunohistochemical techniques. In addition, the binding of antibodies against synthetic peptides representing unique sequences of residues in the products of the trk and trkB protooncogenes was analyzed. These genes encode membrane spanning proteins, which have been shown to constitute specific high affinity binding sites for several members of the nerve growth factor family of neurotrophic factors. The results of the present study imply that the ventral root afferents comprise several different types of sensory axons, which all contain SP-, CGRP-, GAP-43-, and p75NGFr-like immunoreactivities. In addition, at least some of the presumed sensory fiber bundles in ventral roots and the pia mater were immunoreactive for the trkB gene product. Moreover, leptomeningeal cells and nonneuronal cells of the ventral roots were shown to bind antibodies to both the trk and trkB gene products. The ventral root afferents seem to share their immunohistochemical pattern with pain-transducing axons at some other locations, such as the tooth pulp. The contents of SP- and CGRP-LI in sensory axons that reach the central nervous system (CNS) through the ventral root indicate that ventral root afferents may be involved in sensory mechanisms, such as the ventral root pain reaction, as well as in the control of the pial blood vessels. The demonstration of GAP-43 and neurotrophin receptor-immunoreactivities associated with unmyelinated fibers in ventral roots and the pia mater is discussed in relation to previous reports on postnatal plasticity in these axonal populations.
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PMID:Substance P-, calcitonin gene-related peptide, growth-associated protein-43, and neurotrophin receptor-like immunoreactivity associated with unmyelinated axons in feline ventral roots and pia mater. 751 Jul 31

Rats with streptozotocin-induced diabetes of 4 to 6 weeks duration showed a depletion of both substance P (P < 0.01) and calcitonin gene-related peptide (P < 0.01) in the sciatic nerve. Since expression of both peptides is sensitive to nerve growth factor (NGF) in vitro we examined the effect of treatment of diabetic rats with NGF, which significantly increased the levels of both peptides in treated diabetic animals (P < 0.01 for both). Treatment of non-diabetic rats with a similar NGF regime raised the mean peptide levels to a value similar to that seen in treated diabetic rats but the change was not statistically significant. In vehicle-treated diabetic rats the depletions of sciatic nerve neuropeptides were accompanied by a significant (P < 0.05) reduction in the level of CGRP mRNA in the 4th and 5th lumbar dorsal root ganglia, this was accompanied by an analogous reduction in the mRNA for gamma-preprotachykinin A (gamma-PPT), which did not attain statistical significance. Treatment of diabetic rats with NGF also prevented the deficits in the levels of CGRP and gamma-PPT mRNA in the lumbar dorsal root ganglia (P < 0.05). Treatment of other diabetic rats with the related neurotrophin, brain-derived neurotrophic factor (BDNF), had no effect on the levels of substance P and calcitonin gene-related peptide in the sciatic nerve.
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PMID:Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor. 751 41

Neuropeptides were examined for their effects on the survival of cultured rat superior cervical ganglion cells after acute deprivation of nerve growth factor (NGF). Vasoactive intestinal peptide (VIP, 3 microM) delayed the neuronal death about 6 h alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mM) greatly potentiated its effect, reducing EC50 from 2.5 microM to 8 nM. The neuronal death was completely suppressed under this condition. On the other hand, substance P (1-100 microM) or enkephalin (1-100 microM) alone did not modify the death, whereas the latter (100 microM) enhanced the survival-promoting effect of membrane depolarization with elevated K+. These results suggest strongly that neuropeptides regulate the NGF-independent survival of sympathetic neurons through a cAMP-dependent mechanism.
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PMID:Vasoactive intestinal peptide suppresses neuronal cell death induced by nerve growth factor deprivation in rat sympathetic ganglion cells in vitro. 751 83

Using reverse transcription followed by polymerase chain reaction, we examined the expression of mRNA for the tyrosine kinase receptors trk and trkB in rat sensory and sympathetic ganglia during postnatal development. While the levels of both trk and trkB mRNA in the dorsal root ganglia (DRG) decreased two-fold, they increased by seven and two times, respectively, in superior cervical ganglia. The developmentally regulated and tissue-specific expression of trk and trkB genes suggest that peripheral ganglia differ in their responsiveness to neurotrophins in neonatal and adult rats. We found that the temporal pattern of trk expression in DRG neurons correlates with the observed age-dependent ability of nerve growth factor to induce the biosynthesis of the neuropeptide substance P.
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PMID:Postnatal ontogeny of the neurotrophin receptors trk and trkB mRNA in rat sensory and sympathetic ganglia. 751 36

Adult rat dorsal root ganglion sensory neurons in culture require nerve growth factor for synthesis of substance P and calcitonin gene-related peptide but express vasoactive intestinal peptide independently of nerve growth factor. In contrast, the same neurons from newborn rats do not express detectable vasoactive intestinal polypeptide when cultured with nerve growth factor. To further explore the mechanisms regulating neuropeptide expression in these cells, I compared the effects of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, ciliary neurotrophic factor and leukaemia inhibitory factor on substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and somatostatin expression in rat dorsal root ganglion cultures. As with neurons from adult animals, newborn rat sensory neurons required nerve growth factor for synthesis of substance P and calcitonin gene-related peptide. This effect was independent of neuronal survival since most neurons capable of expressing these peptides appeared to survive without added neurotrophic factors. Neurons surviving in the absence of nerve growth factor also expressed vasoactive intestinal polypeptide, suggesting that nerve growth factor suppresses vasoactive intestinal polypeptide expression in immature neurons. However, nerve growth factor withdrawal after eight days' culture failed to cause vasoactive intestinal polypeptide induction which therefore appears to depend on other factors also. Neither ciliary neurotrophic factor nor leukaemia inhibitory factor affected peptide levels when used alone, but both inhibited nerve growth factor-stimulated expression of substance P and calcitonin gene-related peptide in adult rat neurons. They also stimulated vasoactive intestinal polypeptide expression in newborn rat neurons in the presence of nerve growth factor but not to such high levels as those seen under conditions of nerve growth factor deprivation. Neither brain-derived neurotrophic factor nor neurotrophin-3 affected peptide expression significantly. Somatostatin was defected in adult rat neurons, but was unaffected by neurotrophic factors. No somatostatin was detected in newborn rat neurons. These results suggest that in immature animals at least, the increased expression of vasoactive intestinal polypeptide seen in sensory neurons following peripheral nerve injury in vivo, could result from deprivation of target-derived nerve growth factor in combination with increased availability of ciliary neurotrophic factor or leukaemia inhibitory factor from the injured nerve.
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PMID:Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors. 751 8

To study why neonatal and young rats are resistant to the effects of some secretagogues, such as compound 48/80 and 2.5-S nerve growth factor, we examined peritoneal mast cells from 14-15-day-old rats (young rats) and compared them to peritoneal mast cells from adults. Peritoneal mast cells from young rats contain approximately one-tenth of the amount of histamine observed in adult peritoneal mast cells. However, both cell populations contained similar low levels of the mucosal mast cell-associated protease rat mast cell protease II. Histochemical analysis of peritoneal mast cells from young rats using safranin O and berberine sulphate suggested that only a portion of the granules of these cells contained heparin. At an ultrastructural level the young rat peritoneal mast cell contains relatively few granules. The majority of mast cells from young rats have a bilobed or indented nucleus which is only rarely observed in adult cells. Functionally, the young rat peritoneal mast cell demonstrates a significantly reduced histamine release in response to the connective tissue mast cell-specific secretagogues compound 48/80 and 2.5-S nerve growth factor. In contrast, the percent histamine release in response to the neurotransmitter substance P, which degranulates both connective tissue mast cells and intestinal mucosal mast cells, was similar in the adult cells and the young rat cells. This study demonstrates substantial differences between the young rat and adult peritoneal mast cells which may explain the ability of very young animals to withstand large doses of certain secretagogues.
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PMID:Morphological and functional characteristics of peritoneal mast cells from young rats. 752 Mar 64

The expression of three enteric neuropeptides was examined in freshly dispersed ganglia and in ganglia cultured for up to 28 days. During culture, glial cells grew into a flat sheet surrounding a cluster of neurons identified with neuron-specific enolase (13 +/- 2/ganglion), which remained constant throughout the period of culture. The neurons underwent a distinctive temporal change, resulting in overexpression of substance P (SP), normal expression of somatostatin, and virtual suppression of vasoactive intestinal peptide (VIP). Three weeks after the start of culture, the ganglia contained and released (in response to 55 nM KCl, 0.1 mM 1,1-dimethyl-4-phenylpiperazinium, or 1 microM gastrin-releasing peptide) twice as much SP as freshly dispersed ganglia, corresponding to a sevenfold increase per cultured neuron; content and release of somatostatin did not change. SP content and release declined to 1.5% of those found in control cultures when nonneuronal cells were suppressed with cytosine arabinoside but were partially restored (13-17% of control) by nerve growth factor. In marked contrast, VIP was minimally (< 1%) present in and released from ganglia after the third day in culture. Suppression of VIP could reflect a selective loss of VIP neurons and/or VIP expression.
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PMID:Differential expression of substance P, somatostatin, and VIP in neurons from cultured myenteric ganglia. 752 Nov 37

The GH inbred Wistar rat possesses reduced numbers of sympathetic motor neurons. In the present study, we report that substance P (SP) concentrations in superior cervical ganglion, spinal cord, iris and trachea of GH rats are about two-fold those in normal rats, and that SP-containing sensory neuron numbers are elevated in GH rats. These data suggest increased perinatal survival of SP neurons in the GH strain, due to reduced competition by sympathetic neurons for limited amounts of nerve growth factor. By contrast with the situation in iris and trachea, we found no difference between GH and normal rats in SP content of ear skin, atrium or stomach. This accords with previous findings that only some SP sensory neurons are responsive to nerve growth factor.
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PMID:Increased numbers of substance P-containing sensory neurons in a rat strain with a genetic neurotrophic defect. 752 77

Experimental inflammation produced by an intraplantar injection of complete Freund's adjuvant results in local sensory hypersensitivity and up-regulates the neuropeptides substance P and calcitonin gene related peptide in the primary sensory neurons innervating the inflamed tissue. The inflammation also elevates nerve growth factor levels in the skin. Systemic administration of anti-NGF neutralizing antibodies prevent the behavioral sensitivity, the up-regulation of neuropeptides and the inflammation-induced expression of the immediate early gene c-fos in dorsal horn neurons, without modifying swelling and erythema. Elevation of the neurotrophin NGF in the periphery is a major contributor, therefore, of inflammatory pain.
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PMID:Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. 753 Mar 42


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