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)

This study examined the effect of neonatal administration of capsaicin on nociceptive threshold and the distribution of calcitonin gene-related peptide (CGRP), substance P (SP), and fluoride-resistant acid phosphatase (FRAP) in the dorsal horn of the spinal cord during the course of development (10 days to 12 weeks of age) in the rat. As early as 10 days of age, CGRP-like immunoreactivity was reduced in laminae I, II, and V, as well as in the bundles of fibers situated dorsal and ventral to the central canal. However, beginning on or about 6 weeks of age, the density of CGRP-like immunoreactivity in the superficial laminae and in the bundles dorsal and ventral to the central canal increased. Moreover, thick, nonvaricose CGRP-like immunoreactive fibers appeared in laminae III and IV. These recurring fibers were of primary afferent origin as demonstrated by their disappearance after multiple, unilateral rhizotomies. A similar age-dependent alteration in the density of FRAP activity was also observed. Although virtually absent at 10 days of age after neonatal administration of capsaicin, the density of FRAP activity increased in lamina II by 8 weeks of age. This activity disappeared after multiple, unilateral rhizotomies, indicating that the FRAP activity that reappeared was of primary afferent origin. Neonatal administration of capsaicin also reduced the density of SP-like immunoreactivity in the dorsal horn as early as 10 days of age, although the density of SP-like immunoreactivity showed some recovery after 6 weeks of age. However, unlike CGRP-like immunoreactivity or FRAP activity, the density of SP-like immunoreactivity in capsaicin-treated rats was not detectably altered by multiple, unilateral rhizotomies, indicating that it originated principally from intrinsic dorsal horn neurons. Age-dependent alterations in both thermal and mechanical, but not chemical, nociceptive thresholds were also observed in these same animals. Thus, tail flick latency, hot plate latency, and paw withdrawal threshold were maximally increased at 6 weeks of age, after which time thresholds declined to vehicle-treated values. In contrast, capsaicin-treated animals were uniformly insensitive to ophthalmic administration of capsaicin. The correspondence between developmental alterations in CGRP-like immunoreactivity or FRAP activity and in thermal and mechanical nociceptive thresholds is suggestive of a role of CGRP- or FRAP-containing primary afferents in thermal and mechanical nociception.
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PMID:Developmental alterations in nociceptive threshold, immunoreactive calcitonin gene-related peptide and substance P, and fluoride-resistant acid phosphatase in neonatally capsaicin-treated rats. 172 Oct 77

Light and electron microscopic immunohistochemical techniques were used to investigate the central projections and colocalization relationships of a subpopulation of primary afferent neurons that were immunolabelled with an antibody (AB893) against rat liver gap junctions. In lumbar dorsal root ganglia AB893-immunoreactivity was seen in 14.5% of all cells and in both small and large size neurons. Colocalization analysis showed that 78% of all AB893-immunoreactive (AB893-IR) neurons contained calcitonin gene-related peptide, while only 7 to 10% contained the calcium binding proteins parvalbumin or calbindin D28k. Among small type B AB893-IR ganglion cells, it was calculated that over 90% contained fluoride-resistant acid phosphatase, while only 1 to 2% contained substance P or somatostatin. Cytochrome oxidase histochemistry revealed light staining in the vast majority of AB893-IR cells. In the dorsal horn of the spinal cord the antibody labelled fibers in the dorsal root, Lissauer's tract, lamina I and lamina II. Isolated immunoreactive fiber bundles were arranged in sheets spanning most of lamina II. Immunoreactive fibers were depleted from the dorsal horn after dorsal rhizotomy or neonatal capsaicin treatment. Ultrastructural examination showed that AB893-IR fibers were composed of closely associated clusters of 2 to 5 unmyelinated fibers each ranging from 0.1-0.4 microns in diameter. Immunoreactivity was distributed intermittently along the cytoplasmic membrane of axons and en passant sinusoid terminals located centrally within the fiber clusters, as well as along axonal membranes adjacent to the central axon or terminal. The results suggest that the immunoreactive fibers in lamina II of the dorsal horn originate from a subpopulation of AB893-IR neurons that contain FRAP and give rise to unmyelinated axons.
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PMID:Cytochemical relationships and central terminations of a unique population of primary afferent neurons in rat. 193 3

In mature rat sensory neurons, expression of the gene for the growth-associated protein, GAP43, was studied by in situ hybridization with a cDNA probe. Among neurons in normal lumbar dorsal root ganglia, labeling for GAP43 mRNA was heterogeneous, approximately one-half of the neurons being densely labeled. To characterize the latter population, individual neurons were examined in adjacent sections processed either for GAP43 hybridization or NGF-receptor radioautography. Virtually all neurons with high-affinity NGF binding sites had high basal levels of GAP43 mRNA and most GAP43-positive neurons bore NGF receptors. Another NGF-responsive population, sympathetic neurons in the superior cervical ganglion, also had high basal concentrations of GAP43 mRNA. Further co-localization studies in dorsal root ganglia were performed with immunohistochemistry for somatostatin and enzyme histochemistry for acid phosphatase. The latter 2 groups of sensory neurons have been previously shown to lack high-affinity receptors and were here shown to have low basal concentrations of GAP43 mRNA. From this and earlier studies, it can be assumed that substance P-immunoreactive neurons and strongly positive CGRP neurons synthesize GAP43 at high basal rate. One week following peripheral nerve transection, almost all neurons had high concentrations of GAP43 mRNA without correlation with NGF binding. Intrathecal infusion of NGF after the sciatic nerve was cut did not strongly influence this post-traumatic elevation in GAP mRNA. In normal dorsal root ganglia, neurons that have high-affinity NGF binding sites and are therefore potentially responsive to NGF also have high basal rates of synthesis of GAP43.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between GAP43 and nerve growth factor receptors in rat sensory neurons. 215 65

Sensory neurons of adult rat lumbar dorsal root ganglia were labeled in cryostat sections with antisera against tyrosine hydroxylase (TH), substance P (SP), and somatostatin (SOM), and with a monoclonal antibody (RT97) that labels the 145- and 200-kilodalton (kd) subunits of neurofilaments. These neurons were also histochemically stained for fluoride-resistant acid phosphatase (FRAP), and the size and distribution of each population were determined. In addition, the double-label immunoperoxidase technique of Sternberger and Joseph (Sternberger, L.A., and S.A. Joseph (1979) J. Histochem. Cytochem. 27: 1424-1429) was employed to determine whether these antibodies labeled distinct or overlapping populations of neurons. The results indicate that the dopaminergic (TH+) cells constitute a separate population from the SP+ and SOM+ neurons and that the size distributions of the SP+, SOM+, TH+, and FRAP+ cells are all different despite the fact that all of these subpopulations are part of the "small dark" subpopulation as indicated by their size and by the fact that they are RT97-. RT97 is a putative marker for the "large light" population (Anderton, B., H.B. Coakham, J. A. Garson, A.A. Harper, and S.N. Lawson (1982) J. Physiol. (Lond.) 334: 97-98P). Furthermore, the distribution data indicate that all of the "small dark" cell subpopulations are not evenly distributed within the ganglion, and the staining with RT97 and with another antibody which recognizes the 68-kd neurofilament subunit indicates heterogeneity among the "large light" population. These results are discussed in terms of the significance of the "small dark"-"large light" classification.
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PMID:An immunohistochemical and quantitative examination of dorsal root ganglion neuronal subpopulations. 241 May 79

The neuronal population of dorsal root ganglia in mouse consists of various classes of ganglion cells which may be divided in turn into subclasses by using several criteria. In class A cells, membrane-bound organelles are distributed ubiquitously throughout the large perikarya. Subclass A alpha (12%), which is characterized by large clumps of Nissl substance separated by narrow strands of neuroplasm, lacks detectable carbonic anhydrase activity. Subclass A beta (16%) displays small clusters of Nissl substance isolated by broad channels of neuroplasm and a moderate activity of carbonic anhydrase. Subclass A gamma (8%) shows the most intense carbonic anhydrase activity and a lack of uptake for [3H]L-glutamine. In class B cells (63%), the small perikarya display a zonal distribution of the organelles. Subclass B alpha contains parallel cisternae of rough endoplasmic reticulum and acid phosphatase isoenzymes present in long and curved Golgi saccules. Subclass B beta displays straight Golgi saccules rich in acid phosphatase isoenzymes and a high affinity uptake for glutamine. Subclass B gamma is characterized by the absence of acid phosphatase isoenzymes and by the presence of substance P-immunoreactivity. Class C cells (1%) have the smallest size and the highest affinity uptake for glutamine. Thus subtypes of primary sensory ganglion cells may be identified by the concomitant use of multiple criteria.
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PMID:Neuronal subpopulations in the dorsal root ganglion of the mouse as characterized by combination of ultrastructural and cytochemical features. 241 65

The distribution of adenosine deaminase-containing neurons and fibers in the spinal cord and medulla was examined and the relationship of dorsal root ganglia neurons containing this enzyme to those containing somatostatin, substance P, fluoride-resistant acid phosphatase (FRAP) and 5'-nucleotidase was determined using immunohistochemical and histochemical methods. In the spinal cord adenosine deaminase-immunoreactive fibers and neurons were confined to layer I and IIo. A similar localization of these was observed in the spinal trigeminal nucleus. In adult animals treated neonatally with capsaicin adenosine deaminase-positive fibers were totally depleted in layer IIo but only partially depleted in layer I. Analysis of lumbar sensory ganglia revealed that small type-B neurons immunoreactive for adenosine deaminase were also immunoreactive for somatostatin but not substance P. In addition, adenosine deaminase-positive neurons lacked histochemical reaction-product for FRAP and exhibited the lowest activity of 5'-nucleotidase. Examination of the neuronal populations containing the two phosphatase enzymes showed that a proportion of neurons exhibiting 5'-nucleotidase activity were devoid of FRAP activity. It is concluded that dorsal root ganglia neurons immunoreactive for adenosine deaminase and somatostatin constitute a single subpopulation of type-B ganglion cells separate from those containing substance P or FRAP. It appears that the lack of coexistence of adenosine deaminase with either FRAP or 5'-nucleotidase cannot be attributed simply to a coexistence of the two latter enzymes since some 5'-nucleotidase-positive neurons lacking FRAP were also devoid of adenosine deaminase-immunoreactivity. Insofar as these three enzymes may contribute to the regulation of transmission processes in primary sensory neurons, our results indicate a minimal functional relationship between adenine nucleoside and nucleotide degrading enzymes in these neurons. In addition, FRAP appears to have some functional independence from 5'-nucleotidase.
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PMID:Anatomical and cytochemical relationships of adenosine deaminase-containing primary afferent neurons in the rat. 241 72

Cell surface carbohydrates are thought to play important roles in the development and differentiation of mammalian cells. In previous studies we have found that one population of dorsal root ganglion (DRG) neurons is specified by the expression of complex globoseries oligosaccharides (Dodd, J., D. Solter, and T. M. Jessell (1984) Nature 311: 469-472; Jessell, T. M., and J. Dodd (1985) Philos. Trans. R. Soc. Lond. (Biol.) 308: 271-281). We now report that monoclonal antibodies (MAbs) directed against backbone structures of lactoseries oligosaccharides define antigens present in the cytoplasm of a second, anatomically and functionally distinct subset of DRG neurons. Lactoseries carbohydrate structures identified by MAb A5 are restricted to small- and intermediate-diameter DRG neurons with central projections in the superficial dorsal horn of the rat spinal cord. The distribution of labeled terminals suggests that many of the DRG neurons that express lactoseries carbohydrates are likely to convey nociceptive information. More complex galactose- and fucose-substituted lactoseries structures recognized by MAbs LD2, KH10, TC6, TD10, LA4, and anti-Lewis a are segregated on subsets of DRG neurons that differ in their expression of substance P, somatostatin, and fluoride-resistant acid phosphatase and in their laminar termination in the superficial dorsal horn. The majority of lactoseries carbohydrate antigens identified in the cytoplasm of DRG neurons are also expressed on the surface of subsets of DRG neurons in culture. These studies establish that structurally defined carbohydrate differentiation antigens specify the majority of primary sensory neurons with cutaneous receptive fields. Moreover, lactoseries carbohydrate structures similar or identical to those expressed on neonatal DRG neurons in culture have been implicated in cell-cell interactions at early stages of preimplantation embryonic development. Our observations suggest strategies for testing the hypothesis that carbohydrates present on the surface of subsets of DRG neurons play a role in cell interactions that contribute to the laminar organization of sensory afferents in the developing spinal cord.
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PMID:Lactoseries carbohydrates specify subsets of dorsal root ganglion neurons projecting to the superficial dorsal horn of rat spinal cord. 241 92

Peripheral nerve section or local capsaicin application produces depletion of substance P and an enzymatic marker, fluoride-resistant acid phosphatase (FRAP), from circumscribed regions of the terminal areas in the spinal cord. We have made use of this phenomenon to map the extent of central termination of subpopulations of primary afferent neurons containing substance P (SP), somatostatin (SOM), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP) and FRAP in the rat lumbar spinal cord following sciatic nerve section at midthigh level under ether anaesthesia. Between 2 days and 1 year postoperatively, the animals were perfused transcardially and SP, CCK, VIP and SOM were localised in frozen transverse sections of spinal cord segments L1 to S2 and their corresponding ganglia using unlabelled antibody immunohistochemistry. FRAP was localised using a modified Gomori method. SP, SOM, CCK and FRAP were maximally depleted from identical restricted areas of the dorsal horn of the third, fourth and fifth lumbar segments fifteen days after nerve section and remained so for a year. In contrast, VIP staining increased dramatically in the areas from which the other markers were depleted and showed the same time course. Moreover, a large number of neurons in the corresponding ganglia showed positive VIP immunoreactivity after axotomy but were absent from the unoperated side.
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PMID:Vasoactive intestinal polypeptide increases in areas of the dorsal horn of the spinal cord from which other neuropeptides are depleted following peripheral axotomy. 242 58

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

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.
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PMID:Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus. 243 14


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