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)

The production of substance P and the mRNA encoding its precursor (preprotachykinin, PPT) is regulated by nerve growth factor (NGF) in dorsal root ganglion (drg) neurons. To explore the mechanism by which NGF regulates the production of PPT mRNA, we have transfected PC12 cells and F11 cells with plasmids containing the bovine PPT promoter linked to the reporter gene chloramphenicol acetyltransferase (CAT). We have identified (i) functional elements within the PPT promoter which are necessary for expression in the absence of NGF and (ii) two separate regions, each of approximately 250 bp, which confer NGF responsiveness. Both regions contained a sequence element, similar to a known transcription factor binding site, which is present in several other NGF-regulated genes.
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PMID:Identification of nerve growth factor-responsive sequences within the 5' region of the bovine preprotachykinin gene. 174 55

Hybrid cell lines derived from neonatal rat dorsal root ganglia neurons fused with the mouse neuroblastoma N18Tg2 exhibit sensory neuron-like properties not displayed by the parental neuroblastoma. These properties include an inward (depolarizing) current with a conductance increase in response to activation of a bradykinin receptor, an inward (depolarizing) current with a conductance increase in response to the sensory excitotoxin capsaicin, the expression of sensory neuropeptides (substance P, CGRP and somatostatin), the expression of phosphatidylinositol-anchored molecules including adhesion molecules of the immunoglobulin superfamily that can be regulated in serum-free culture by nerve growth factor (N-CAM, F-3 and Thy-1), and low permissivity to herpes simplex virus infection. These lines thus provide appropriate models for the study of mechanisms involved in nociceptor activation and the regulation of expression of sensory-neuron specific markers including neuropeptides.
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PMID:Novel cell lines display properties of nociceptive sensory neurons. 197 43

The changes in gene expression and protein synthesis induced in neurons by axotomy usually lead to increased production of axon constituents and decreased production of molecules related to neurotransmission. Exceptions to this generalization occur, however, and it is unclear whether the injury itself changes the pattern of synthesis or whether individual mechanisms regulate the synthesis of the various axonal components. We used in situ hybridization histochemistry and immunocytochemistry to compare the changes in L4 and L5 rat dorsal root ganglion neuron levels of preprotachykinin mRNA and tachykinin peptides caused by sciatic nerve injury with those caused by dorsal root injury. Both lesions elicit regeneration, although only the axotomized peripheral processes re-establish functional contact with their targets. In the contralateral, intact dorsal root ganglia approximately 17% of neurons contained detectable levels of both mRNAs and peptides. Sciatic nerve section decreased by 70% the number of neurons labeled for preprotachykinin mRNA at three days post-operatively. Not all cells in the ganglion are axotomized by the sciatic nerve lesion; grain counts over the cells spared by the lesion showed an increased level of labeling, possibly a result of collateral sprouting by these spared cells. By two weeks, the number of cells labeled for preprotachykinin mRNA had decreased to 80% of control levels. The numbers of neurons labeled for tachykinin peptides decreased more slowly and reached approximately 50% of control numbers at two weeks. By six months post-operatively, when regeneration is largely complete, the number of neurons containing both mRNAs and peptides returned to normal. In contrast, dorsal root section did not elicit a decrease in the number of neurons labeled either for the mRNAs or the peptides at any of the post-operative intervals examined. These results indicate that axotomy is not the stimulus that elicits changes in the expression of genes coding for tachykinins. Evidence is considered indicating that interruption of the supply of peripherally derived nerve growth factor may be responsible for the changes in gene expression for tachykinins after axotomy.
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PMID:Expression of beta-preprotachykinin mRNA and tachykinins in rat dorsal root ganglion cells following peripheral or central axotomy. 209 25

Changes in the innervation of the cardiovascular system, urinogenital tract and sympathetic and non-sympathetic ganglia have been examined following long-term sympathectomy. Patterns of innervation were investigated using histochemical and immunohistochemical techniques, while levels of noradrenaline and neuropeptides were measured by neurochemical assays. Large doses of guanethidine (50 mg/kg) were given daily for 3 weeks to 8-day-old rat pups, which were killed at 6 or 20 weeks of age. In both age groups noradrenergic nerves were severely depleted or absent, while in some regions dramatic increases of calcitonin gene-related peptide levels were demonstrated. This was revealed by an increase in the density of nerve fibres and in calcitonin gene-related peptide content (up to 18-fold), most notably in the right atrium and superior cervical ganglion. No changes in substance P- or vasoactive intestinal polypeptide-immunolabelled nerves were seen. Conversely, short-term sympathectomy by 6-hydroxy-dopamine treatment caused a depletion of noradrenaline which was not accompanied by an increase in the number or content of calcitonin gene-related peptide-immunolabelled nerves. The possibility that nerve growth factor is involved in the mechanism of hyperinnervation by calcitonin gene-related peptide-containing sensory nerves following long-term sympathectomy is discussed.
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PMID:Marked increases in calcitonin gene-related peptide-containing nerves in the developing rat following long-term sympathectomy with guanethidine. 211 38

Hepatocytes in suspension, freshly isolated from meal-fed rats, were used to study the acute influence of growth factors on the rate of de novo fatty acid synthesis. Nerve growth factor (2.5 S) and epidermal growth factor caused a substantial increase in the rate of fatty acid synthesis, whereas fibroblast growth factor was inhibitory. Little effect was observed with nerve growth factor (7 S), bombesin or substance P. Transferrin did not affect hepatic fatty acid synthesis. The results are discussed in relation to the effects of insulin and tumor-promoting phorbol esters.
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PMID:Differential short-term effects of growth factors on fatty acid synthesis in isolated rat-liver cells. 241 54

Interactions between peptidergic sensory nerves, noradrenergic sympathetic nerves, and cholinergic parasympathetic fibers were examined in the rat iris. The putative peptide neurotransmitter, substance P (SP), was used as an index of the trigeminal sensory innervation, tyrosine hydroxylase (TH) activity served to monitor the sympathetic fibers, and choline acetyltransferase (CAT) activity was used as an index of the parasympathetic innervation. Destruction of the sympathetic innervation by neonatal administration of 6-hydroxydopamine resulted in increased SP development and a smaller increase in CAT activity in the iris. Moreover, trigeminal ablation resulted in an increase in both TH and CAT activities. Finally, ciliary ganglionectomy resulted in increased SP and a smaller increase in TH activity in the iris. Administration of nerve growth factor (NGF) into the anterior chamber substantially increased both SP and TH activity in the iris and also increased CAT activity to a lesser extent. Moreover, administration of anti-NGF into the anterior chamber prevented both the sympathectomy-induced increases in SP and CAT, and the increases in TH and CAT activities after trigeminal ablation, suggesting that NGF mediated these increases. These observations suggest that the sympathetic, sensory, and parasympathetic innervations of the iris interact by altering availability of NGF elaborated by the iris. Regulation of iris CAT activity was examined in greater detail. Injection of the cholinergic toxin, AF64A, into the anterior chamber concurrently with ablation of the sympathetic and sensory innervations paradoxically increased CAT activity, whereas AF64A alone decreased CAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parasympathetic, sympathetic, and sensory interactions in the iris: nerve growth factor regulates cholinergic ciliary ganglion innervation in vivo. 241 84

Mechanisms regulating peptidergic, noradrenergic and cholinergic development were compared in dissociated cell cultures of neonatal rat sympathetic ganglia. The majority of cultured neurons contained at least two neurotransmitters and many neurons contained three or more. These studies were undertaken to determine whether co-existing transmitters were co-ordinately regulated by the environment. Co-culture of sympathetic neurons with ganglion non-neuronal cells increased substance P and choline acetyltransferase activity but decreased somatostatin and tyrosine hydroxylase activity. Conversely, elimination of non-neuronal cells virtually abolished neuronal expression of substance P and choline acetyltransferase and increased somatostatin and tyrosine hydroxylase. Consequently, under these conditions, somatostatin and tyrosine hydroxylase were similarly regulated, whereas substance P was associated with choline acetyltransferase. By contrast, stimulation of adenylate cyclase or treatment with membrane-permeable adenosine 3',5'-phosphate analogs increased tyrosine hydroxylase and decreased choline acetyltransferase, but had no effect on substance P or somatostatin levels. Moreover, potassium- or veratridine-induced membrane depolarization increased tyrosine hydroxylase but decreased substance P, somatostatin and norepinephrine levels. However, inhibition of neurotransmitter release with magnesium or calcium-free medium prevented the decrease in norepinephrine levels but not the decrease in substance P and somatostatin. Consequently, the effects of membrane depolarization on peptide levels cannot be ascribed to release and subsequent depletion of substance P and somatostatin and must result from decreased net synthesis (synthesis minus catabolism) of the transmitters. Nerve growth-factor treatment also differentially regulated transmitter metabolism; nerve growth factor increased protein-specific activities of tyrosine hydroxylase and choline acetyltransferase but did not increase the protein-specific content of substance P and somatostatin. Quantitative transmitter expression was also influenced by neuron density; increasing density elevated substance P and choline acetyltransferase activity but decreased somatostatin and tyrosine hydroxylase activity per neuron. Finally, culture of sympathetic neurons in a defined (serum-free) medium also altered some but not all traits, decreasing substance P, somatostatin and choline acetyltransferase without any change in tyrosine hydroxylase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential regulation of peptide and catecholamine characters in cultured sympathetic neurons. 241 73

Whether or not adrenal medullary (chromaffin) cells which respond to nerve growth factor (NGF) both in vitro and in vivo require NGF for their normal development is controversial. Systemic deprivation of endogenous NGF by injection of anti-NGF antibodies into rat fetuses or by transfer of anti-NGF to the offspring of autoimmunized mothers has provided conflicting results. We have reinvestigated the effects of a specific antiserum to NGF on the morphology, catecholamine (CA) and neuropeptide (Met-enkephalin, Met-ENK; substance P, SP) content, and choline acetyltransferase (ChAT) activity of the rat adrenal medulla. Fetuses were injected with anti-NGF antibodies on day 17 of gestation and postnatally at daily intervals for 7 days. The histological appearance of adrenal medullae of anti-NGF injected animals was not altered as compared to controls. Ultrastructurally, no degenerative changes or developmental retardation of chromaffin cells could be detected. However, numbers of chromaffin granules per micron 2 of cytoplasmic area were greater and the mean diameters of the cores of adrenaline storage granules were smaller in antibody-treated than in control animals. CA and SP content, ratios of adrenaline to noradrenaline and ChAT activities were identical in anti-NGF-treated and control animals. Anti-NGF antibodies caused a reduction of adrenal Met-ENK by 40% as compared to controls. Superior cervical ganglia from the same animals were used to document immunosympathectomy induced by the antiserum. They displayed the well-established structural alterations and a marked reduction of the CA content. We conclude that administration of anti-NGF antibodies to embryonic and early postnatal rats induces only subtle changes in the ultramorphology of chromaffin cells without altering the development of normal CA levels. The small, yet significant effects of anti-NGF antibodies on adrenal Met-ENK, however, may suggest a role for endogenous NGF in the regulation of opioid peptide metabolism in developing chromaffin cells.
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PMID:Effects of pre- and postnatal administration of antibodies to nerve growth factor on the morphological and biochemical development of the rat adrenal medulla: a reinvestigation. 242 96

The apomorphine-induced inhibition of histamine release in rat peritoneal mast cells was studied by means of secretagogues stimulating different pathways of mast cell activation. Apomorphine inhibited the mast cell response to all releasing agents (lysophosphatidylserine plus nerve growth factor, compound 48/80, substance P, ATP, tetradecanoylphorbolacetate, melittin). The IC50 ranged from 4 microM to 24 microM at concentrations of secretagogues releasing 30-50% of mast cell histamine. However, the potency of the drug decreased at higher secretagogue concentrations. Mast cells, pretreated with apomorphine and washed, released little histamine upon stimulation. The secretory response could be partially restored on increasing the concentration of secretagogues. The results suggest that apomorphine affects a regulatory step controlling the terminal sequence of mast cell secretory activity. As indicated by the reduced potency of the drug, the control by the apomorphine-sensitive reaction loses efficiency under conditions of massive histamine release.
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PMID:Apomorphine-induced inhibition of histamine release in rat peritoneal mast cells. 242 81

Neuropeptides are found in specific subpopulations of primary afferent neurones. Peptide expression can be altered following axotomy or under the influence of nerve growth factor. Here we have examined the consequence of altering the peripheral target of afferent neurones. Many unmyelinated afferents from skin contain substance P-like immunoreactivity (SPLI) whilst those from muscle do not. We have found that fibres will innervate inappropriate tissue types. We have therefore cut and cross-anastomosed a skin and muscle hindlimb nerve in the rat and 10-12 weeks later analysed the regenerated nerves immunocytochemically for SPLI. Muscle afferents inappropriately reinnervating skin were found to contain many SPLI fibres in contrast to control nerves resutured to their own distal stumps. Conversely, skin afferents made to innervate muscle showed reduced levels of peptide staining. These results demonstrate the plasticity of peptide expression and suggest that factors in peripheral tissue or perhaps distal nerve sheaths exert a trophic influence on nervous system function.
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PMID:Peptide expression is altered when afferent nerves reinnervate inappropriate tissue. 243 99


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