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)

Rat sciatic nerves were treated with tetrodotoxin (TTX) for 4--10 days, by implanting a glass capillary tube filled with TTX into the nerve through the epineurium. Following this treatment the somatotopic organization of receptive fields in the L4 dorsal horn, an area of cord normally responding only to foot stimulation. The map was normal in animals treated with TTX. Dorsal horn levels of fluoride-resistant acid phosphatase, substance P, somatostatin, cholecystokinin-like peptide, neurotensin and neurophysin were also normal as assessed from density of staining. These results are discussed in the light of the positive changes that are seen following chronic sciatic nerve section.
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PMID:Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat. 628 71

The importance of nerve growth factor (NGF) for the development of sensory ganglia was investigated by injecting rat fetuses (16.50 days of gestation) with a single dose of anti-NGF antiserum. Four months later the treated animals showed a very large decrease in substance P- and somatostatin-like immunoreactivities in dorsal root ganglia and skin with a lesser decrease in trigeminal ganglia. Fluoride-resistant acid phosphatase, substance P-, and somatostatin-like immunoreactivities were greatly decreased in the dorsal horn of the spinal cord. No change in neurotensin- and [Met]enkephalin-like immunoreactivities was observed. The anti-NGF antiserum treatment produced a greater than 90% decrease in the number of unmyelinated dorsal root fibers and a 35% decrease in the total number of myelinated fibers. The loss in myelinated fibers was restricted to small-diameter fibers with no change in large-diameter fibers. No change in taste bud morphology was noted, thereby refuting the proposal that anti-NGF antiserum treatment may represent an animal model for familial dysautonomia. The present results indicate that NGF is a necessary requirement for the normal development of a significant population of prenatal rat dorsal root ganglion cells.
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PMID:Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia. 660 28

The isolectin B4 from Griffonia simplicifolia I binds to a subpopulation of rat small-diameter dorsal root ganglion neurons, and to fibres and presumed terminals in laminae I-II of the spinal cord dorsal horn. In the present study we investigated B4 and B4 conjugated to horseradish peroxidase as potential transganglionic tracers of somatic primary afferent neurons after injection into a peripheral nerve. We also tried to identify the specific subpopulation of dorsal root ganglion neurons that bind and ganglion neurons that bind and transport B4. Following injection of B4 or B4-horseradish peroxidase into the sciatic nerve, labelled presumed terminals that reached peak labelling at two days were found exclusively in regions of the spinal cord gray matter known to receive unmyelinated primary afferent fibres. Almost all dorsal root ganglion cells that transported B4-horseradish peroxidase also bound B4. Cell counts showed that 51% of the dorsal root ganglion neurons were B4-positive and cell area measurements that these were all in the small size range. An extensive overlap was found between B4 and fluoride-resistant acid phosphatase (85%), and between B4 and calcitonin gene-related peptide (59%). Seventeen per cent of the B4-positive cells were substance P-immunoreactive and 9% were immunoreactive to somatostatin. Minimal overlap was seen between B4-positive cells and cells positive for RT97 (3%), a selective marker of primary afferent neurons with myelinated axons. All somatostatin-immunoreactive cells and almost all (95%) of the fluoride-resistant acid phosphatase-positive cells were contained within the B4-positive population. This comprised also 58% of the cells immunoreactive to calcitonin gene-related peptide and 42% of those immunoreactive to substance P. The results obtained show that B4 binds to a subpopulation of unmyelinated primary afferent neurons, and that B4 and B4-horseradish peroxidase can be used as selective transganglionic tracers of this specific cell subpopulation.
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PMID:Transganglionic transport and binding of the isolectin B4 from Griffonia simplicifolia I in rat primary sensory neurons. 753 Mar 47

Neutral endopeptidase 24.11 (NEP; "enkephalinase") may inactivate a number of centrally active neuropeptides including the enkephalins and substance P. In most areas of the central nervous system, the cell types which express NEP activity are not known. The hypoglossal nucleus (N.XII) was selected as a model system to characterize the cytochemical localization of NEP. The effect of hypoglossal nerve axotomy upon the distribution of NEP activity in the hypoglossal nucleus was compared to the effect upon cholinergic markers, the mu opiate receptor, and the enkephalins. By use of a fluorescence histochemical method, NEP was localized at all levels of N.XII to the soma and proximal processes of the majority of the apparent motor neurons in the nucleus. Fluorescent double-labeling studies revealed the presence of numerous enkephalinergic varicosities which localized to the neuropil surrounding NEP-stained motor neurons. To determine whether NEP was synthesized by these motor neurons, 18 rats received a unilateral transection of the hypoglossal nerve. A pronounced decrease in NEP staining in N.XII was observed on the operated side as early as 3 days following axotomy. This decrease persisted at all levels of the nucleus for about 5 weeks. By 7 weeks, the staining between the control and operated sides was indistinguishable. By contrast, there was no apparent change in the density or distribution of enkephalin-immunoreactive varicosities in five animals examined 6 to 32 days following axotomy. Radioligand binding of [3H]DAMGO to the mu-opiate receptor in N.XII was studied in 20 animals by quantitative autoradiography at 2, 6, and 11 days after axotomy. No significant changes in the level of radioligand binding to the mu-receptor were detected in response to axotomy. In contrast to the opiate system, the cholinergic enzymes choline acetyltransferase, acetylcholinesterase, and pseudocholinesterase showed a coordinate decrease in motor neuron-associated staining on the operated side of N.XII at 3, 6, and 11 days following axotomy which paralleled the decrease in NEP staining. By contrast, the lysosomal enzyme marker, acid phosphatase, showed a pronounced increase in staining on the operated side. The results of this study are consistent with the synthesis of NEP by cholinergic N.XII motor neurons and indicates that the enkephalins and NEP in N.XII are closely associated, but derive from separate neuronal populations. The widespread overlap in the distribution of NEP-stained motor neurons and enkephalinergic varicosities in N.XII provides additional anatomical support for a potential role for NEP in the inactivation of centrally active enkephalins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential response of neutral endopeptidase 24.11 ("enkephalinase"), and cholinergic and opioidergic markers to hypoglossal axotomy. 820 Oct 16

The localization of catechol-O-methyltransferase immunoreactivity in rat dorsal root ganglia and in the spinal cord and its co-existence with substance P, calcitonin gene-related peptide and fluoride-resistant acid phosphatase in dorsal root ganglion cells was examined with immunohistochemical and histochemical double-staining methods. Analysis of dorsal of dorsal root ganglia at both cervical and lumbar levels revealed catechol-O-methyltransferase immunoreactivity in numerous dorsal root ganglion cells. Double-staining studies showed that catechol-O-methyltransferase and substance P immunoreactivities were located in different cells with a few exceptions, whereas both catechol-O-methyltransferase and calcitonin gene-related peptide immunoreactivities were detected in about 10% of all labeled cells positive for one of the two markers at both levels studied. The great majority of fluoride-resistant alkaline phosphatase-positive cells were also immunoreactive for catechol-O-methyltransferase. Again, no difference was found between cervical and lumbar levels. Catechol-O-methyltransferase immunoreactivity was also found in the neuropil of the dorsal horn of the spinal cord. The staining was most intense in the superficial laminae (I-III) and overlapped partly with substance P and calcitonin gene-related peptide immunoreactivity. Western blotting analysis revealed that soluble catechol-O-methyltransferase was the clearly dominating form of the enzyme in dorsal root ganglia. The distribution pattern of catechol-O-methyltransferase in dorsal horn and sensory neurons suggests that the enzyme may modulate sensory neurotransmission.
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PMID:Catechol-O-methyltransferase in rat sensory ganglia and spinal cord. 878 48

The author examined the adrenal glands of rats that were kept in a workshop of an NPK fertilizer factory for 30 days and then for 60 days in the laboratory. Histochemical examination of the reticular zone revealed an increase in neutral lipids and triglycerides and a decrease in phospholipids. The nucleic acid content, predominantly RNA, was enhanced. Although the acid phosphatase activity was slightly lowered, both succinate dehydrogenase and monoamine oxidase activities were increased. The results indicate that exposure of rats to NPK fertilizer had a stimulating effect on the reticular zone of their adrenal glands.
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PMID:The reticular zone of the rat adrenal gland 60 days after exposure to a chemical fertilizer. 886 29

In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.
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PMID:Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder. 972 57

The conventional tritiated thymidine (3H-TdR) incorporation assay is considered as the 'gold standard' for the assessment of cell growth. However, the 3H-TdR incorporation assay has several disadvantages which have prompted the development of nonradiolabelling proliferation assays such as 5-bromo-2-deoxyuridine (BrdU) ELISA, tetrazolium microplate assay and acid phosphatase assay. In studies, these three proliferation assays have shown equivalent sensitivity and reproducibility to the 3H-TdR incorporation assay. However the results may be affected by the cell type studied. In the present study, we have used these three proliferation assays for the assessment of rat lymph node CD4 + T lymphocyte growth in response to polyclonal antigen stimulation. The proliferation assays were compared on the basis of four criteria: sensitivity, reproducibility, stimulation index and insensitivity of the assay to the cell number. Our results indicated that the BrdU ELISA demonstrated the highest sensitivity, reproducibility and stimulation index but had a limited linear range for cellular growth. The tetrazolium microplate assay also had a relatively good sensitivity, reproducibility, stimulation index and a wider linear response range for cell growth in comparison to the BrdU ELISA. The acid phosphatase assay showed the lowest reproducibility and stimulation index. Because BrdU incorporation in DNA of proliferating cells has been reported to block cell division, we have investigated this possibility in sequential assays. Our results indicated that in our experimental conditions no evidence of an anti-mitogenic action of BrdU was observed. We also compared the performance of the MTS assay and BrdU ELISA in measuring substance P-induced CD4 + T cell proliferation. The results indicated that the MTS assay may reflect change in cell activation leading to an overestimate of cell growth. In conclusion, our results indicate that the BrdU ELISA is the most sensitive of the three proliferation assays used for the assessment of CD4 + T lymphocyte growth and is the preferred assay when small changes in cell growth are expected.
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PMID:Suitability of cell metabolic colorimetric assays for assessment of CD4+ T cell proliferation: comparison to 5-bromo-2-deoxyuridine (BrdU) ELISA. 1008 97

The possibility that the nervous system may control bone metabolism has been raised, as neuromediators physiologically conveyed by sympathetic fibers (eg, vasoactive intestinal peptide) influence bone resorption in vitro. In this study, the sympathetic system was inactivated by treating rats with guanethidine (40 mg/kg/day), a sympathetic neurotoxic, for 21 days, after which a wave of osteoclastic resorption was induced along the mandibular buccal cortex. The effects of denervation were assessed 4 days later (corresponding to the peak of resorption in this model). The rats exhibited ptosis soon after starting guanethidine, proving the success of the sympathectomy. This was associated with a significant increase in calcitonin gene-related peptide- (+54%, p < 0.02) and substance P-immunoreactive sensory fibers (+29%,p < 0.02), a known effect of sympathectomy. For the quantitation of the bone parameters, the study zone was divided into a juxta-osseous alkaline phosphatase-positive osteogenic compartment and a nonosteogenic compartment. In the osteogenic compartment, the resorption surface was reduced by 56% (p < 0.001) in the treated animals, together with a fall in the number of osteoclasts (-25%,p < 0.05) and impaired osteoclast access to the bone surface. Tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear preosteoclasts were found only in this compartment; they were reduced by 43% (p < 0.05) by the sympathectomy. No change in non-specific esterase (NSE)+ osteoclast precursors was found. In the nonosteogenic compartment, vasodilation was the only effect of sympathectomy (+80%,p < 0.05); in particular, the number of NSE+ cells was not modified. Our results indicate that: (1) interactions of NSE+ precursors with osteogenic cells are required for their differentiation into TRAP+ preosteoclasts; (2) the sympathetic nervous system is not involved in osteoclast precursor recruitment; but (3) has a significant effect on resorption by inhibiting preosteoclast differentiation and disturbing osteoclast activation. These data suggest that depletion of sympathetic mediators may disturb osteogenic cell-mediated osteoclast differentiation.
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PMID:Chemical sympathectomy impairs bone resorption in rats: a role for the sympathetic system on bone metabolism. 1057 74

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and muscarinic toxins, in Dendroaspis venoms, and acetylcholinesterase in other elapid venoms, is to promote hypotension. Venom dipeptidyl peptidase IV-like enzymes probably also contribute to hypotension by destroying vasoconstrictive peptides such as Peptide YY, neuropeptide Y and substance P. Purines apparently bind to other toxins which then serve as molecular chaperones to deposit the bound purines at specific subsets of purine receptors. The assignment of pharmacological activities such as transient neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to purines bound to these toxins, and/or to free venom purines.
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PMID:Ophidian envenomation strategies and the role of purines. 1173 31


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