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 mechanisms underlying the severe urinary retention induced by acrylamide intoxication were studied in detail in the rat. Subcutaneous treatment with acrylamide monomer (50 mg/kg daily for 10 days) almost completely impaired the micturition reflex, resulting in urinary retention. In fact, the ability to eliminate an oral water load was virtually abolished, while bladder filling with saline (transvesical cystometrogram) failed to activate reflex micturition. Instead, a picture of overflow incontinence resulted in urethane-anaesthetized rats, which was not reversed by intravenous administration of 4-aminopyridine. The nerve-mediated contractile response to field stimulation (0.1-20 Hz, 0.5 ms, 60 V) of the isolated bladder was unaffected, thus suggesting the integrity of bladder efferent innervation, and no evidence was found from in vitro experiments that the myogenic contractility of the bladder was depressed by acrylamide treatment. Conversely, the sensory nerve-mediated response to capsaicin was abolished and sensory nerve fibres of the bladder were selectively depleted of their content of substance P- and calcitonin gene-related peptide immunoreactivity following acrylamide treatment. In fact, concentrations of the same neuropeptides in other organs, including the adjoining ureters, were unaffected. As to the urethral segment, including the striated sphincter, the D-tubocurarine (0.2 mM)-sensitive urethral response to electrical stimulation (0.1 Hz, 0.1 ms, 20 V) was significantly reduced in acrylamide-treated animals. At the same level, neurofilament protein immunostaining revealed striking accumulations of neurofilament protein-like material in motor end-plates, thus indicating that neuromuscular junctions of the urethral striated sphincter were severely affected. Thus, the afferent arm of the micturition reflex was shown to be severely deranged by acrylamide intoxication, especially in its capsaicin-sensitive component. Since twitch-like contractions of the urethral striated sphincter are probably involved in promoting bladder voiding, a decreased efficiency of this mechanism could participate in the picture of urinary retention induced by acrylamide.
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PMID:Acrylamide-induced visceral neuropathy: evidence for the involvement of capsaicin-sensitive nerves of the rat urinary bladder. 164 5

A reduction in the supply of retrogradely transported NGF has been proposed as a possible signal for the axotomy response in dorsal root ganglion (DRG) neurons. Components of the axotomy response that have previously been well characterized in axotomized DRG cells include changes in cytoskeletal gene expression and changes in the expression of neurotransmitters/neuromodulators such as substance P. In this study, we examined the role of NGF in the axotomy response by examining protein synthesis and mRNA levels of the low-MW neurofilament protein (NF-L) and beta-tubulin in DRG cells at 1, 7, and 12 d after axotomy with and without continuous administration of exogenous NGF. We also examined substance P levels in the DRG by immunocytochemistry under the same experimental conditions. Sciatic nerves of adult male rats were unilaterally transected at the midthigh level, and the proximal nerve stumps were placed into Silastic tubes connected to osmotic minipumps that were filled with biologically active NGF. NGF (0.5 mg/ml in saline) was continuously infused (0.5 microliter/hr) onto the proximal stumps of transected sciatic nerves for 1-12 d. Control animals were prepared in an identical fashion except that the nerves were treated with saline alone. At death, DRGs were removed from the animals; the L4 experimental DRGs (axotomized) and contralateral L4 DRGs (uninjured) were used immediately for protein synthesis experiments, while the experimental and contralateral L5 DRGs were fixed in 4% paraformaldehyde and subsequently used for in situ hybridization and immunocytochemistry. From another set of experimental animals, the L4 and L5 DRGs were harvested and used for total RNA isolation and RNA blotting experiments. Immunocytochemical studies using a polyclonal antibody to substance P showed that the immunodetectable levels of this peptide decreased to undetectable levels in DRG neurons after axotomy and saline administration. However, in axotomized neurons treated with NGF, the level of immunodetectable substance P did not decrease, but instead, increased over even that present in normal DRG neurons. Pulse labeling of DRGs with 35S-methionine:cysteine followed by 2-dimensional (2D) gel electrophoresis and fluorography revealed that the synthesis of neurofilament (NF) proteins was decreased, while that of tubulin was increased, 12 d after sciatic nerve transection. NGF administration to axotomized neurons did not alter this pattern. Quantitative analysis of in situ hybridizations of DRG neurons and RNA blot analysis with cDNA probes specific for NF-L and beta-tubulin mRNAs showed that NGF treatment of axotomized DRGs did not significantly affect cytoskeletal gene expression at the mRNA level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:NGF rescues substance P expression but not neurofilament or tubulin gene expression in axotomized sensory neurons. 170 53

Immunoreactivity for calretinin, a calcium-binding protein, was studied in neurones in the guinea-pig small intestine. 26 +/- 1% of myenteric neurones and 12 +/- 3% of submucous neurones were immunoreactive for calretinin. All calretinin-immunoreactive neurones were also immunoreactive for choline acetyltransferase and hence are likely to be cholinergic. In the myenteric plexus, two subtypes of Dogiel type-I calretinin-immunoreactive neurones could be distinguished from their projections and neurochemical coding. Some calretinin-immunoreactive myenteric neurones had short projections to the tertiary plexus, and hence are likely to be cholinergic motor neurones to the longitudinal muscle. Some of these cells were also immunoreactive for substance P. The remaining myenteric neurones, immunoreactive for calretinin, enkephalin, neurofilament protein triplet and substance P, are likely to be orad-projecting, cholinergic interneurones. Calretinin immunoreactivity was also found in cholinergic neurones in the submucosa, which project to the submucosal vasculature and mucosal glands, and which are likely to mediate vasodilation. Thus, calretinin immunoreactivity in the guinea-pig small intestine is confined to three functional classes of cholinergic neurones. It is possible, for the first time, to distinguish these classes of cells from other enteric neurones.
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PMID:Calretinin immunoreactivity in cholinergic motor neurones, interneurones and vasomotor neurones in the guinea-pig small intestine. 171 38

Immunoreactivity for the neurofilament protein triplet was investigated in neurons of the dorsal root ganglia of the guinea-pig by using a battery of antibodies. In unfixed tissue, nearly all neurons in these ganglia demonstrated some degree of neurofilament protein triplet immunoreactivity. Large neurons generally displayed intense immunoreactivity, whereas most small to medium-sized neurons showed faint to moderate immunoreactivity. Double-labelling immunofluorescence demonstrated that most antibodies to the individual subunits of the neurofilament protein triplet had the same distribution and intensity of labelling in sensory neurons. Increasing durations of tissue fixation in aldehyde solutions selectively diminished neurofilament protein triplet immunoreactivity in small to medium-sized neurons. Double-labelling with neurofilament protein triplet antibodies in combination with antibodies to other neuronal markers, such as neuron-specific enolase, substance P and tyrosine hydroxylase, showed that tissue processing conditions affect the degree of co-localization of immunoreactivity to the neurofilament protein triplet and to these other neuronal markers. These results indicate that, with a judicious manipulation of the duration of tissue fixation, neurofilament protein triplet immunoreactivity can be used in combination with other neuronal markers to distinguish groups of neurons according to their size and chemical coding.
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PMID:Neurofilament protein triplet immunoreactivity in the dorsal root ganglia of the guinea-pig. 171 54

It is well established that acetylcholine is a neurotransmitter at several distinct sites in the mammalian enteric nervous system. However, identification of the cholinergic neurons has not been possible due to an inability to selectively label enteric cholinergic neurons. In the present study an immunohistochemical method has been developed to localize choline acetyltransferase, the synthetic enzyme for acetylcholine, in order that cholinergic neurons can be visualized. The morphology, neurochemical coding and projections of cholinergic neurons in the guinea-pig small intestine were determined using double-labelling immunohistochemistry. These experiments have revealed that many myenteric neurons are cholinergic and that they can be distinguished by their specific combinations of immunoreactivity for neurochemicals such as calretinin, neurofilament protein triplet, substance P, enkephalin, somatostatin, 5-hydroxytryptamine, vasoactive intestinal peptide and calbindin. On the basis of their previously described projections, functional roles could be attributed to each of these populations. The identified cholinergic neurons are: motorneurons to the longitudinal muscle (choline acetyltransferase/calretinin); motorneurons to the circular muscle (choline acetyltransferase/neurofilament triplet protein/substance P, choline acetyltransferase/substance P and choline acetyltransferase alone); orally directed interneurons in the myenteric plexus (choline acetyltransferase/calretinin/enkephalin); anally directed interneurons in the myenteric plexus (choline acetyltransferase/somatostatin, choline acetyltransferase/5-hydroxytryptamine, choline acetyltransferase/vasoactive intestinal peptide); secretomotor neurons to the mucosa (choline acetyltransferase/somatostatin); and sensory neurons mediating myenteric reflexes (choline acetyltransferase/calbindin). This information provides a unique opportunity to identify functionally distinct populations of cholinergic neurons and will be of value in the interpretation of physiological and pharmacological studies of enteric neuronal circuitry.
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PMID:Immunohistochemical identification of cholinergic neurons in the myenteric plexus of guinea-pig small intestine. 172 93

The peripheral reorganization of pulpal nerves after tooth injury was studied, in the rat, with anterograde horseradish peroxidase tracing techniques, and combined retrograde Fluorogold tracing and immunohistochemistry was employed to examine the effects of inferior alveolar nerve lesions or tooth injury on some cytochemical characteristics of pulpal trigeminal ganglion nerve cells, namely content of substance P, calcitonin gene-related peptide and the ganglioside GM1 (binding subunit of cholera toxin), as well as affinity to RT 97 (antibody to neurofilament protein) and the lectin Griffonia simplicifolia isolectin I-B4. Anterograde horseradish peroxidase tracing demonstrated that pulpal nerves either disappear or reinnervate novel targets after loss of pulpal tissue. There were no obvious signs of neuroma formation. Retrograde Fluorogold labelling with immunohistochemistry showed that after inferior alveolar nerve lesions with subsequent regeneration, a much higher proportion of Fluorogold cells (15%) were substance P-positive compared to normal (2%). In addition, 3% of the cells were Griffonia simplicifolia isolectin I-B4-positive. Such cells were very rare in controls. Proportions of calcitonin gene-related peptide-, GM1- and RT-97-positive cells were normal. After tooth lesions, the proportions of Fluorogold-positive substance P-, Griffonia simplicifolia isolectin I-B4-, GM1- and RT 97-labelled cells were similar to controls, while the proportion of calcitonin gene-related peptide-positive neurons was reduced. The results show that pulpal deafferentation may change the long-term cytochemical characteristics of affected trigeminal ganglion neurons.
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PMID:Anterograde horseradish peroxidase tracing and immunohistochemistry of trigeminal ganglion tooth pulp neurons after dental nerve lesions in the rat. 192 70

The Edinger-Westphal (EW) nucleus, also known as the accessory oculomotor nucleus in the chick, provides the cholinergic preganglionic input to the parasympathetic ciliary ganglion. In addition to acetylcholine, many EW neurons have been shown to contain enkephalin-like and/or substance P-like immunoreactivity. Establishment of EW neurons in culture would make possible study of their interactions with ciliary ganglion neurons in vitro and in addition would provide a valuable system for studying cholinergic/peptidergic neurons of the vertebrate central nervous system. We describe here dissociated cell cultures established from midbrain tissue containing the EW nucleus. In these cultures, 86% of the cells with neuronal morphology were positive for intracellular acetylcholinesterase activity, 54% were positive for enkephalin-like immunoreactivity, and 4% were positive for substance P-like immunoreactivity. The proportions of neurons that scored as labeled were even higher if the number of positive cells was compared to the number of cells in sister cultures immunoreactive for the large neurofilament protein polypeptide. When the cultures were stained simultaneously for acetylcholinesterase activity and enkephalin-like immunoreactivity, 34% of the cells with neuronal morphology were positive for both. In cultures derived from adjacent tissue regions very few cells expressed both activities. These results suggest that the cells expressing both acetylcholinesterase activity and enkephalin-like immunoreactivity in culture are EW neurons. The putative EW neurons survive for weeks in vitro in the absence of their normal target, the ciliary ganglion.
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PMID:Preganglionic neurons from the Edinger-Westphal nucleus: growth and histochemical characterization in cell culture. 241 24

In rat L5 dorsal root ganglia 50% of neurons contained arginine vasopressin-like immunoreactivity and 38% oxytocin-like immunoreactivity, the oxytocin entirely coexisting with the arginine vasopressin. Staining of alternate mirror-image sections with RT97 (an antibody to neurofilament protein, and a marker for large light neurons) and with arginine vasopressin antiserum showed that the two were entirely complementary, thus establishing arginine vasopressin as a marker for all small dark neurons. Mirror-image staining also showed that neurons containing substance P-like immunoreactivity and those containing fluoride-resistant acid phosphatase activity were each contained within the arginine vasopressin-positive population. Arginine vasopressin-like immunoreactivity was axonally transported in the dorsal root and (in greater quantity) in sciatic nerve. Arginine vasopressin-like immunoreactivity was present also in laminae I and II of the dorsal horn of the spinal cord and this reactivity was absent in animals which had been treated neonatally with capsaicin, suggesting that it was contained in primary afferent terminals. These results are discussed in terms of their implications for the classification of primary afferent neurons and of a possible physiological role for arginine vasopressin in these neurons.
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PMID:A quantitative analysis of the interrelationships between subpopulations of rat sensory neurons containing arginine vasopressin or oxytocin and those containing substance P, fluoride-resistant acid phosphatase or neurofilament protein. 242 33

Neural crest, taken from cephalic and trunk levels of quail embryos, was grown in vitro in conventional tissue culture medium (Dulbecco's modified Eagle's medium containing 15% fetal calf serum and either 2 or 15% chick embryo extract (CEE] or in a chemically defined serum- and CEE-free medium. Depending on the conditions employed, different types of neuronal or neuronlike cells developed in the cultures. Thus, in medium containing 15% CEE, adrenergic cells (identified by tyrosine hydroxylase immunoreactivity and catecholamine histofluorescence) emerged after 5-6 days. These cells lacked tetanus toxin binding sites and did not react with an antibody directed against 70-kDa neurofilament protein. In the fully defined medium, a neuronal cell type exhibiting neurofilament and substance P (SP) immunoreactivity differentiated from noncycling precursors within 1 or 2 days of culture. If serum was added to the medium, the neurites disintegrated and the neuronal cells ultimately died. By sequentially culturing neural crest, first in the wholly synthetic medium for 1-3 days and then in the conventional medium supplemented with serum and 15% CEE, the disappearance of the SP-positive neurons was followed, several days later, by the emergence of adrenergic cells. The majority of these cells and/or their precursors were found to undergo cell division in culture. We conclude that the cells expressing the adrenergic phenotype (characteristic of the sympathetic nervous system) and those displaying SP immunoreactivity, comparable to a category of neurons in dorsal root and cranial sensory ganglia, derive from distinct sets of precursors. Our results reinforce the contention, deduced from in ovo transplantation experiments (see N. M. Le Douarin, (1984) In Cellular and Molecular Biology of Neuronal Development (I. Black, Ed.), pp. 3-28. Plenum, New York), that at least two lineages, from which sensory and autonomic cell types are derived respectively, are segregated early during neural crest ontogeny and have extremely different survival and trophic requirements.
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PMID:Cell lineages in peripheral nervous system ontogeny: medium-induced modulation of neuronal phenotypic expression in neural crest cell cultures. 243 74

The rostral parts of the cephalic neural plate and neural crest of mice, stage Theiler 12, were prepared and cultured. At that stage of development they exclusively consist of proliferative ventricular cells, which do not yet display vimentin and neurofilament immunoreactivity. 3H-thymidine autoradiography showed that the progenitor cells of neurons became postmitotic as soon as they were taken into culture. The neurofilament protein (kD 68) was immunocytochemically demonstrable from day 2 in culture, while immunoreactivity to vimentin was never observed. The neurons, prematurely developed from the neuroepithelium of stage Theiler 12-embryos, were identified by their histological and immunocytochemical properties. They gave distinct patterns of immunoreactivity to neuropeptides and anti-serotonin antibodies. Anti-serotonin and anti-somatostatin antibodies reacted from the 3rd day of culture. Antibodies against ACTH, luliberin, substance P and vasopressin gave positive reactions at day 7. Two classes of neurons, the serotonin and the large substance P-immunoreactive ones, were recognized by both immunoreactivity and morphology. The serotonin immunoreactive neurons usually were of a multipolar shape and had a long, varicose axon that was heavily stained, particularly at its distal third. The perikarya appeared in limited areas of the cultured tissue. They grew in the vicinity of each other, but never in densely packed aggregates. The large neurons, reacting heavily with antibodies against substance P and faintly with all the other neuropeptide antibodies applied, were up to 50 micron in diameter and usually occurred in 20-40 cells per preparation of half a neural plate. The results suggest that at least some classes of neurons can develop from the cultured neural plates of stage Th12.
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PMID:Ventricular cells from the mouse neural plate, stage Theiler 12, transform into different neuronal cell classes in vitro. 244 39


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