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 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

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

Many receptors stimulate proliferation of NIH 3T3 cells in a ligand dependent fashion. Based on this observation, we developed a high throughput assay of cloned receptor pharmacology. In this assay, receptors are transiently co-expressed with the marker enzyme beta-galactosidase. Receptors that induce cellular proliferation select and amplify the cells that also express the marker, thus the ability of ligands to alter receptor activity are reported as changes in enzyme activity. In the present study, we used this assay to evaluate the ability of agonist ligands to stimulate four cloned receptors. The agonists phenylephrine, carbachol, substance P and nerve growth factor selectively stimulated cells transfected with the alpha-1b adrenergic, m4 muscarinic, NK1 neurokinin and trkA neurotrophin receptors, respectively. These data demonstrate that a high throughput colorimetric assay performed in 96 well plates can be used to evaluate the pharmacology of ligands for cloned receptors belonging to a wide range of functional and pharmacological classes.
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PMID:High throughput assays of cloned adrenergic, muscarinic, neurokinin, and neurotrophin receptors in living mammalian cells. 756 80

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

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

We have previously reported the isolation of an EGF-responsive precursor from the embryonic and adult mouse striatum. This precursor exhibits self renewal and the ability to produce a sphere of undifferentiated cells which can be induced to differentiate into neurons and glia. RT-PCR analysis of these spheres of undifferentiated cells revealed the expression of mRNA for the trkB neurotrophin receptor, both with and without the catalytic domain, and little or no expression of trkA or trkC. We examined the actions of BDNF on the fate of EGF-generated neural precursors. Ten days after a one-time exposure to BDNF, single EGF-generated spheres showed a twofold increase in neuron number and a marked enhancement in neurite outgrowth. Examination of neuronal nuclei with immunochemical probes for c-fos and bromodeoxyuridine revealed that the actions of BDNF were directly upon neuronal cells and did not involve division of neuronal precursors. The twofold increase in neuronal number due to BDNF, observed after 10 d in vitro, was significantly reduced after 21 d in vitro and was not apparent at 27 d in vitro. Quantitative analyses revealed that while repeated application of BDNF did not prevent the loss of neuron number over time, it did result in a significant increase in neurite numbers. Moreover, delayed addition of BDNF mimicked the increase in neuronal numbers seen when BDNF was present throughout. These BDNF actions did not appear to involve the enhancement of a novel neuronal phenotype, with all effects being due to increase in the numbers and neurite outgrowth of neurons that colocalize GABA and substance P. These findings suggest that BDNF markedly enhances the antigenic and morphologic differentiation of EGF-generated neuronal precursors. BDNF alone does not appear to act as a survival factor for neuronal precursors nor is it sufficient for preventing their death over time.
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PMID:BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors. 764 17

The effects of unilateral extramandibular inferior alveolar nerve injury on pulpal blood-flow responses to electrical stimulation and i.v. injections of substance P (SP) in cat mandibular canine teeth with a dentinal lesion were investigated with laser Doppler flowmetry. After blood-flow recordings, the teeth were fixed and the pulps were examined with light and electron microscopy. The distribution of pulpal SP, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), growth-associated protein (GAP-43) and low-affinity neurotrophin receptor (LANR)-like immunoreactivity was examined with immunohistochemical fluorescence microscopy. Blood-flow recordings, performed at 10 days and 1 month postoperatively, showed that vasodilation, occurring in control teeth after bipolar electrical stimulation of the tooth crown, was absent in the denervated pulps, whereas at 3 months, five of six teeth had regained responsiveness, although at a low level. There was enhanced vasodilation (by 370%) to SP injections (400 fmol i.v.) at 10 days in denervated pulps. Such supersensitivity was reduced at 1 month despite the apparent lack of nerve fibers, and the response fell further towards the level in control teeth at 3 months when pulpal axons reappeared. At 10 days and 1 month postoperatively, light and electron microscopy demonstrated that surgery had resulted in total pulpal denervation. At 3 and 6 months, a large number of regenerated pulpal axons reappeared, in accordance with previous findings. At 10 days and 1 month after nerve transection immunohistochemistry showed a complete loss of pulpal immunoreactivity to all the neuropeptides that were studied. At 3 and 6 months, neuropeptide immunoreactivity reappeared but far fewer number of pulpal nerve fibers were SP-, NKA- and CGRP-immunoreactive than under normal conditions, as demonstrated by double-labeling experiments with GAP-43- or LANR-antiserum. The results indicate that pulpal hemoregulatory functions, which are lost after denervation, do not return to normal levels after nerve regeneration. This malfunction may be caused by inadequate target re-innervation and/or a deficiency of neuropeptides in the re-innervated pulp.
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PMID:Cat dental pulp after denervation and subsequent re-innervation: changes in blood-flow regulation and distribution of neuropeptide-, GAP-43- and low-affinity neurotrophin receptor-like immunoreactivity. 769 71

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

Expression of mRNAs for the protein tyrosine kinases trk, trkB and trkC, encoding essential components of high-affinity neurotrophin receptors, was studied in the spinal cord and dorsal root ganglion during normal development and in the adult rat following peripheral and central axon injury. Northern blots revealed multiple trkB transcripts in the embryonic, early postnatal and adult spinal cord with different patterns of expression during development. The levels of 9.0 kb and 4.8 kb trkB transcripts, encoding a full-length trkB receptor, increased progressively during embryonic development with maximal levels around birth, followed by a decline at adulthood. In contrast, the level of 7.5/7.0 kb trkB transcripts, encoding a truncated trkB receptor, reached maximal levels shortly after birth and similar levels remained in the adult animal. In the spinal cord a 4.7kb trkC transcript was detected with maximal levels shortly after birth. In situ hybridization revealed a uniform labeling throughout the spinal cord for both trkB and trkC mRNAs with maximal intensities of labeling shortly after birth. The level of the 2.4 kb trkB transcript in the spinal cord increased 5-fold 8 days after a crush lesion of the sciatic nerve or the dorsal root, while no change was seen in the levels of the other trkB transcripts. No change in the 4.7 kb trkC mRNA was seen following these two injuries, although increased levels of several smaller size trkC transcripts were observed. For both trkB and trkC, similar size transcripts as seen in the spinal cord were also detected in adult rat dorsal root ganglia. Consistent with previous observations of decreased levels of cytoskeletal proteins after peripheral and central axotomy, the level of neurofilment light chain mRNA decreased markedly in the dorsal root ganglia following a crush lesion of the sciatic nerve or of the dorsal root. A small decrease was also seen in the level of preprotachykinin-A mRNA encoding the protein precursor of substance P. In the same animals, the levels of all five trkB transcripts increased 3-fold in the dorsal root ganglia in response to these two injuries. A small increase was also seen in the level of trkC mRNA. The level of brain-derived neurotrophic factor (BDNF) mRNA increased two-fold in the dorsal root ganglia following either of the two lesions, while no change was detected in trk mRNA following these two injuries.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy. 851 Apr 96


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