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

Women have a higher incidence of inflammatory disorders than men and also appear to perceive painful stimuli differently. It has been suggested that neuroinflammation plays a role in painful bladder disorders of uncertain etiology, such as interstitial cystitis. Nerve growth factor (NGF) is a neurotrophin produced in peripheral tissues that can also mediate pain and inflammation. We found that treatment of mice with the estrogen antagonist ICI 182,780 had no effect on bladder NGF content but decreased bladder NGF messenger RNA. Using immunohistochemistry, we demonstrated that the mucosa is the primary source of NGF in the mouse bladder, and the bladder mucosa also expresses estrogen receptor (ER)-alpha, ER-beta, and the high-affinity NGF receptor tyrosine kinase A. Estrogen may also modulate neurogenic inflammation by interaction with other substances and cells that participate in the pathogenesis of neurogenic inflammation, including substance P, bradykinin, and mast cells. Collectively, these observations indicate that estrogen has the capacity to influence the onset and course of neurogenic inflammation of the bladder.
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PMID:Estrogen and neuroinflammation. 1137 49

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve-dependent regulation of a substance P-like immunoreactive (SP-ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) did not affect the percent of SP-ir cells in the developing tectum. Treatment with d-(-)-2-amino-5-phosphonovaleric acid (d-AP-5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) produced increases in SP-ir cells in the treated lobes of normal animals, which were significant in the case of NT-4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve-transected tadpoles. These changes in the percent of SP-ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT-4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide-expressing population of cells.
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PMID:Neurotrophins, but not depolarization, regulate substance P expression in the developing optic tectum. 1143 42

Peripheral cranial sensory nerves projecting into the oral cavity receive food intake stimuli and transmit sensory signals to the central nervous system. To describe and compare the features of the cranial sensory ganglia that innervate the oral cavity, i.e., the trigeminal, petrosal, and geniculate ganglia (TG, PG, and GG, respectively), in situ hybridization was conducted using riboprobes for neurotrophin receptors (TrkA, TrkB, and TrkC), a neurotransmitter (substance P), and ion channels important for thermosensation (VR1 and TREK-1). In TG, all in six probes yielded positive signals to various extent in intensity and frequency. In addition, a strong correlation between the expression of VR1 and those of TrkA and substance P was observed as in the case of the dorsal root ganglia. In PG, positive signals to all six probes were also detected, and the correlation of expression was similar to that shown by TG. On the other hand, most cells in GG were positive to the TrkB probe, and a small number of cells were positive to the TrkC probe, but no significant signal was observed for the other four probes. These results indicate that TG and PG consist of cells that are heterogeneous in terms of neurotrophin requirement and somatosensory functions, and that GG seems to consist mainly of a homogeneous cell type, gustatory neurons. In conclusion, TG, PG, and GG, show gene expression characteristics intrinsic to the three ganglia. It is also concluded that TG and a portion of PG project several types of somatosensory nerves. This is consistent with the finding that GG and a portion of PG project gustatory nerves.
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PMID:A comparative study of three cranial sensory ganglia projecting into the oral cavity: in situ hybridization analyses of neurotrophin receptors and thermosensitive cation channels. 1158 88

The ontogeny of gut innervation in the anuran amphibian Xenopus laevis was studied using immunohistochemistry on sections of whole larvae from NF stages 38-52. Immunoreactivity to acetylated tubulin confirmed the presence of nerve fibres as early as stages 38-39. Actin immunoreactivity was found at stage 41, indicating the presence of smooth muscle cells. Trk-like neurotrophin receptors were occasionally found in nerve fibres as soon as stages 38-39. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivities coexisted in nerves innervating the gut wall from stages 40-41, and nitric oxide synthase (NOS) from stage 42. Substance P/neurokinin A (SP/NKA) occurred at stage 42. In all these cases, the first fibres were observed in the oesophagus. Calcitonin gene-related peptide (CGRP) was first observed in nerves at stage 48. In general, VIP/PACAP and NOS innervation was denser than the tachykinin innervation. In conclusion, the development of nerve fibres in the Xenopus gut is probably dependent on neurotrophins that may act via Trk-like receptors and occur before the gut wall is fully organised morphologically. Feeding in Xenopus larvae starts at NF stage 45. The study demonstrates that several of the transmitters investigated are expressed in the gut innervation (and in endocrine cells) prior to this stage.
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PMID:Occurrence of neurotrophin receptors and transmitters in the developing Xenopus gut. 1168 80

Many studies have indicated changes in neuropeptides in inflammatory bowel disease (IBD), but with contradictory results. Nerve growth factor also has a potential role in the maintenance of enteric nerves and may be associated with IBD. A quantitative immunohistochemical method was used to measure area density of immunoreactive nerves in the colonic mucosa of surgical specimens. No significant differences in immunoreactivity for substance P, vasoactive intestinal polypeptide, growth associated protein 43, and the neurotrophin receptor p75 were seen in the control, Crohn's, and ulcerative colitis groups. Compared to age-matched normal colon (N = 18), there was an increase in neutrophil number in Crohn's (P < 0.05) and ulcerative colitis (P < 0.01) (both N = 9). There were positive correlations (P < 0.05) between neutrophil number and growth associated protein, between p75 and substance P immunoreactive nerves in ulcerative colitis, and between p75 and vasoactive intestinal polypeptide in Crohn's specimens. These data indicate a link between the immunologic and nervous systems in IBD.
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PMID:Neuropeptides and nerve growth in inflammatory bowel diseases: a quantitative immunohistochemical study. 1191 10

Huntington's disease is a neurodegenerative disorder characterized by a selective degeneration of striatal projection neurons, which deal with choreic movements. Neuroprotective therapy could be achieved with the knowledge of the specific trophic requirements of these neuronal populations. Thus, the induction of endogenous trophic response or the exogenous administration of neurotrophic factors may help to prevent or stop the progression of the illness. Excitotoxicity has been implicated in the etiology of Huntington's disease, because intrastriatal injection of glutamate receptor agonists reproduces some of the neuropathological features of this disorder. Activation of glutamate receptors in the striatum differentially regulates the expression of neurotrophins, glial cell line-derived neurotrophic factor (GDNF), neurturin, and their receptors in the striatum and in its connections, cortex, and substantia nigra, showing a selective trophic response against excitotoxic insults. Transplantation of cells genetically engineered to release neurotrophic factors in the striatum has been used to study the neuroprotective effects of neurotrophin and GDNF family members in the excitotoxic model of Huntington's disease. Neurotrophins (brain-derived neurotrophic factor [BDNF], neurotrophin-3, and neurotrophin-4) protected striatal projection neurons against quinolinic or kainic acid treatment. However, GDNF family members showed a more specific action. Neurturin only protected gamma-aminobutyric acid (GABA)/enkephalinergic neurons that project to the external segment of the globus pallidus, whereas GDNF exerts its effects on GABA/substance P positive neurons, which project to the substantia nigra pars compacta and the internal segment of the globus pallidus. In conclusion, the trophic requirements of each population of striatal projection neurons are due to a complex interaction between several neurotrophic factors, such as neurotrophins and GDNF family members, which can be modified, in different pathological conditions. Moreover, these neurotrophic factors may be able to provide selective protection for basal ganglia circuits, which are affected in striatonigral degenerative disorders, such as Huntington's disease or multisystem atrophy.
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PMID:Neuroprotection by neurotrophins and GDNF family members in the excitotoxic model of Huntington's disease. 1203 Dec 78

A number of studies have implicated severe infections early in life as a risk factor for the subsequent development of asthma. In particular it has been suggested that respiratory syncytial virus (RSV) infection may enhance the development of "allergic" inflammatory responses when the host is exposed to allergens after an episode of bronchiolitis. It has also been suggested that neuronal mechanisms are important in RSV infection and subsequent airway hyperreactivity. Recently we advanced the hypothesis that immune and neuronal mechanisms may be linked and that combined neuroimmune responses may be in play. In the airways a dense network of sensory nerve fibers is strategically placed just below the epithelial surface so that any change in the bronchial environment may stimulate the release of the proinflammatory neuropeptide substance P. During RSV infection, stimulation of these nerves causes a marked increase in airway vascular permeability over that in pathogen-free rats and results in an increase in overall inflammatory status. Our work has revealed that these changes are mediated by the high affinity receptor for substance P [neurokinin (NK) 1 receptor], the expression of which is greatly increased by RSV. This up-regulation presumably occurs at the gene expression level, as NK1 receptor mRNA levels increase substantially during RSV infection. We have also shown that T lymphocyte subpopulations within the bronchial-associated lymphoid tissue in the lungs of RSV-infected rats express high levels of the NK1 receptor. As a consequence stimulation of the sensory nerves by any airborne irritant has the potential of causing a new inflammatory cycle mediated by NK1 receptor-expressing T lymphocytes attracted into the airways and activated by substance P. This mechanism may establish important neuroimmune interactions, which undergo long term dysregulation after RSV infection and predispose to airway inflammation and hyperreactivity. Finally our most recent studies show that RSV infection promotes a large increase in the expression of nerve growth factor (NGF) and neurotrophin receptors. RSV-induced release of NGF leads to short and long term changes in the distribution and reactivity of sensory nerves across the respiratory tract, participating to exaggerated inflammatory reactions during and after the infection. NGF and its receptors may also amplify other immunoinflammatory and neuronal pathways contributing to airway inflammation and hyperreactivity. On the basis of these observations, we postulate that changes of neurotrophin expression in the respiratory tract may represent an important link between early life viral infections and childhood asthma.
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PMID:Contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection. 1267 55

Although the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output pathways are still awaited. Therefore, we performed quantitative choline acetyltransferase (ChAT) immunocytochemistry to localize major cholinergic nuclei and to determine the number of respective cholinergic neurons in the rabbit forebrain. The density of ChAT-immunoreactive terminals in layer V of distinct neocortical territories and in hippocampal subfields was also measured. Another cholinergic marker, the low-affinity neurotrophin receptor (p75(NTR)), was also employed to identify subsets of cholinergic neurons. Double-immunofluorescence labeling of ChAT and p75(NTR), calbindin D-28k (CB), parvalbumin, calretinin, neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase, or substance P was used to elucidate the neuroanatomical borders of cholinergic nuclei and to analyze the neurochemical complexity of cholinergic cell populations. Cholinergic projection neurons with heterogeneous densities were found in the medial septum, vertical and horizontal diagonal bands of Broca, ventral pallidum, and magnocellular nucleus basalis (MBN)/substantia innominata (SI) complex; cholinergic interneurons were observed in the caudate nucleus, putamen, accumbens nucleus, and olfactory tubercule, whereas the globus pallidus was devoid of cholinergic nerve cells. Cholinergic interneurons were frequently present in the hippocampus and to a lesser extent in cerebral cortex. Cholinergic projection neurons, except those localized in SI, abundantly expressed p75(NTR), and a subset of cholinergic neurons in posterior MBN was immunoreactive for CB and nNOS. A strict laminar distribution pattern of cholinergic terminals was recorded both in the cerebral cortex and in CA1-CA3 and dentate gyrus of the hippocampus. In summary, the structural organization and chemoarchitecture of rabbit basal forebrain may be considered as a transition between that of rodents and that of primates.
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PMID:Rabbit forebrain cholinergic system: morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus. 1271 17

NGF increases expression and content of substance P in developing and mature spinal sensory neurons. The role this neurotrophin plays in peptide release, however, is less clear. Accordingly, we examined substance P release from cultures of mature rat sensory neurons, which do not require NGF for survival. Neurons grown without NGF have a low but detectable basal release, which increases with depolarization by KCI (50 mM) but never achieves statistical significance. In contrast, basal release is 3 times higher from neurons that have been cultured in the presence of NGF, and KCl depolarization triples the amount of SP released. Stimulation with capsaicin (10(-7) M) yields similar results. Residual peptide remaining after capsaicin stimulation is refractory to release for up to 24 h. Bradykinin does not induce SP secretion from mature neurons nor does it potentiate the action of capsaicin. GDNF, which also increases SP content, mimics NGF. Addition of NGF to the bath during release does not directly induce SP secretion, nor does it alter the effects of KCI, capsaicin, or bradykinin. It appears therefore that NGF increases SP release indirectly by increasing intracellular stores.
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PMID:Nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) regulate substance P release in adult spinal sensory neurons. 1271 37

A variety of biological as well as synthetic implants have been used to attempt to promote regeneration into the damaged spinal cord. We have implanted mats made from fibronectin (FN) into the damaged spinal cord to determine their effectiveness as a substrate for regeneration of axons. These mats contain oriented pores and can take up and release growth factors. Lesion cavities 1 mm in width and depth and 2 mm in length were created on one side of the spinal cord of adult rats. FN mats containing neurotrophins or saline were placed into the lesion. Mats were well integrated into surrounding tissue and showed robust well-oriented growth of calcitonin gene-related peptide, substance P, GABAergic, cholinergic, glutamatergic, and noradrenergic axons into FN mats. Transganglionic tracing using cholera toxin B indicated large-diameter primary afferents had grown into FN implants. Schwann cells had also infiltrated FN mats. Electron microscopy confirmed the presence of axons within implants sites, with most axons either ensheathed or myelinated by Schwann cells. Mats incubated in brain-derived neurotrophic factor and neurotrophin-3 showed significantly more neurofilament-positive and glutamatergic fibers compared to saline- and nerve growth factor-incubated mats, while mats incubated with nerve growth factor showed more calcitonin gene-related peptide-positive axons. In contrast, neurotrophin treatment had no effect on PGP 9.5-positive axons. In addition, in some animals with neurotrophin-3-incubated mats, cholera toxin B-labelled fibers had grown from the mat into adjoining intact areas of spinal cord. The results indicate that FN mats provide a substrate that is permissive for robust oriented axonal growth in the damaged spinal cord, and that this growth is supported by Schwann cells.
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PMID:Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat. 1289 49


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