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)

Substance P-like immunoreactivity (SPLI) was localized in the superficial spinal dorsal horn of the rat by means of light and electron microscopic immunocytochemical techniques. Serial immunocytochemical sections were subjected to densitometric measurements with an electronic Image Analyser, and with aid of a computer program, a two-dimensional reconstruction of the fine neuroanatomical structure of the SPLI-active regions of the lumbosacral upper superficial spinal dorsal horn was obtained. SPLI activity in the superficial dorsal horn outlines four well-marked and distinctly differing regions, called, in the mediolateral sequence, areas A, B, C, and D, plus Cajal's noyeau interstitiel ("lateral spinal nucleus" = "nucleus of the dorsolateral fascicle," L). Lumbosacral dorsal rhizotomy results in an almost complete depletion of SPLI from ipsilateral areas A, B, C, and D; it induces decreased SPLI in the area of the lateral spinal nucleus (L), ipsi- or contralaterally in an alternating fashion. Transection of the segmentally related, ipsilateral peripheral nerve induces a marked depletion of SPLI from areas A, B, and C but only a slight decrease in area D and virtually none in the area of L. Whereas a simple crush of the peripheral nerve (axocompression) induces only a slight depletion of SPLI, if any, semiautomatic densitometric analysis of serial immunocytochemical sections proves that a controlled crush injury (axocontusion) results in depletion of SPLI from the upper dorsal horn, similar to transection of the peripheral nerve. Following regeneration of the ipsilateral, segmentally related peripheral nerve, the original immunocytochemical structure of the superficial dorsal horn is re-established by SPLI-positive axonal sprouts originating from previously damaged dorsal root axons.
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PMID:Primary afferent origin of substance P-containing axons in the superficial dorsal horn of the rat spinal cord: depletion, regeneration and replenishment of presumed nociceptive central terminals. 238 13

Sensory nerves innervating rat distal limb skin were labeled by axonal transport of an enzyme-lectin conjugate injected into lumbar dorsal root ganglia (DRG), with emphasis on tracing the course of the thin axons. Selective neonatal neurotoxin destruction of most unmyelinated sensory or sympathetic axons was achieved by treatment with capsaicin (CAP) and 6-hydroxydopamine (6-OHDA), respectively. The relationship of substance P-immunoreactive (SPI) axons to the patterns of axonal transport-labeled thin axons was compared in normal and neurotoxin-treated animals. SPI is restricted to a limited population of unmyelinated axons, and electron-microscopic observation reveals its total absence in myelinated axons. SPI fibers of sensory origin, as determined by CAP susceptibility, can be traced into the epidermal stratum spinosum, in relation to guard hair follicles, mast cells, and a specific class of small blood vessels. These morphological features are not eliminated by neurotoxin sympathectomy, and some are inferred to contribute to the initial events associated with the neurogenic vasodilation and plasma extravasation associated with the inflammatory response. A re-evaluation of the concept of "free nerve endings" is suggested in the context of the variety of afferent and efferent patterns displayed by sensory peptidergic unmyelinated axons, their putative nociceptive role, and the functional diversity of sensory C fibers.
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PMID:Thin-fiber cutaneous innervation and its intraepidermal contribution studied by labeling methods and neurotoxin treatment in rats. 241 70

Neurons surrounding the central canal in sacral spinal segments were functionally characterized on the basis of somatic and/or visceral afferent input, then intracellularly marked with horseradish peroxidase (HRP). Tissue sections containing portions of HRP-stained neurons were subsequently immunohistochemically examined for the presence of contacts made by axonal enlargements containing vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin (SS), Leu-enkephalin (ENK), or serotonin (5-HT). ENK-and 5-HT-containing enlargements were found to contact all neurons examined. SP and SS terminals contacted fewer neurons, and were not associated with specific functional classes. On the other hand, VIP-containing fibers contacted only those neurons receiving visceral afferent input, thus supporting the contention that VIP is contained in a population of visceral afferent fibers projecting to the gray matter surrounding the central canal at sacral levels.
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PMID:Immunohistochemistry of synaptic input and functional characterizations of neurons near the spinal central canal. 241 42

Combined neuroanatomical techniques were used to examine the organization of the striatal projection to the substantia nigra in the rat. Both double anterograde axonal tracing methods (Phaseolus vulgaris leuco-agglutinin (PHA-L) and 3H-amino acid tract tracing) and double fluorescent retrograde axonal transport tracing methods were used to examine the relationship among striatal neurons projecting to separate areas of the substantia nigra. Additionally, the distributions of retrogradely labeled striatonigral projection neurons were charted relative to the neurochemically distinct striatal "patch" compartment, identified by substance P- or leu-enkephalin-like immunoreactivity, and the complementary "matrix" compartment, identified by somatostatin-like immunoreactive fibers. These studies show two distinct types of organization in the striatonigral projections. One type is topographic in that the mediolateral relationships among these striatal efferent neurons are roughly maintained by their termination patterns in the substantia nigra, while the dorsoventral relationships are inverted. Projections from any part of the striatum, however, are distributed throughout the rostrocaudal axis of the substantia nigra. Despite their general topographic organization, the variable and dispersed nature of such projections from individual striatal loci results in partial overlap of afferent fields from separate striatal areas. The second type of organization is nontopographic and provides a different system for convergence of inputs from separated striatal areas that is superimposed on the rough topographic system. In this other projection system the mediolateral and dorsoventral relationships typical of the topographically ordered system are not maintained and are sometimes reversed. For example, PHA-L injected into the dorsal striatum labels a topographic (inverted relationship) projection to the ventral substantia nigra pars reticulata but also a smaller and separate projection to the dorsal pars reticulata and adjacent pars compacta. Retrograde tracer deposits in the pars compacta label neurons in the ventral striatum (the inverted relationship) but also clusters of neurons in the dorsal striatum. These clusters are in the neurochemically defined patch compartment whereas neurons in the matrix are labeled by injections into the pars reticulata. The dendrites of both retrogradely filled patch and matrix neurons are confined to the compartment containing their cell bodies, suggesting a restriction that would functionally segregate extrinsic striatal afferents shown in other studies to be confined to either patches or matrix.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The neostriatal mosaic. I. Compartmental organization of projections from the striatum to the substantia nigra in the rat. 241 39

A wealth of evidence suggests that catecholamines (particularly norepinephrine) influence gonadotropin secretion via a direct interaction with the LHRH neurons. Neuropeptides such as neurotensin (NT) and substance P (SP) are likewise implicated in the control of LHRH secretion, based on pharmacological and preliminary anatomical studies. Since sub-populations of LHRH neurons project to areas of the brain other than the median eminence, a detailed analysis of the topography of axonal interactions of catecholamines (CA), substance P and neurotensin with LHRH cells was conducted in adult male mice using dual immunocytochemical techniques. An analysis of the patterns of apparent contact of NT or SP axons on LHRH cells as determined by close apposition of immunoreactive axons to LHRH cells when viewed under a light microscope at high magnification revealed that the density of NT or SP axons was not a reliable index of the degree of contact; in many locations, NT and SP had similar densities yet a greater portion of the LHRH cells appeared contacted by SP than NT. NT axons were in close contact with up to one-third of the LHRH cells. Analysis of the location of these "contacted" cells did not reveal a discrete subnucleus controlled by NT. Rather, the NT-contacted cells were scattered throughout the LHRH cell field. Interactions of LHRH cells with SP axons were likewise uniform throughout most of the LHRH cell field, with the exception of the most anterior portion of the field. In the anterior septum, few SP axons appeared to contact LHRH cells. Elsewhere, most of the LHRH cells were in contact with SP axons. For the CAs, the fiber density in the regions of the LHRH cells was uniformly moderate, yet the pattern of cells contacted showed variation across the LHRH cell field, with most of the "contacted" cells located near the OVLT and medial preoptic area. These data suggest that LHRH cells may be differentially regulated by NT, SP and the CAs.
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PMID:Organization of LHRH cells: differential apposition of neurotensin, substance P and catecholamine axons. 241 51

Contrary to what would have been expected, an antagonist of substance P (SP) [Arg5,D-Trp7,9]SP-(5-11) inhibited the neurogenic contraction of isolated guinea-pig hilus bronchi more readily than a contraction produced by exogenous SP. Furthermore, it has previously been shown that a tachykinin antagonist given intrathecally produced motor blockade as do local anaesthetic drugs. We therefore examined whether tachykinin antagonists had a depressant action on axonal neurotransmission. The compound action potential (APc) of the frog isolated sciatic nerve was suppressed in a concentration-dependent manner by the tachykinin antagonists [D-Pro2,D-Trp7,9]SP and [Arg5,D-Trp7,9]Sp-(5-11), both being about 4 times more potent than lidocaine. SP itself was without effect. Similarly in the rat isolated sciatic nerve [D-Pro2,D-Trp7,9]SP suppressed the APc. It was more potent in the A alpha- than in the C-fibres. SP did not affect conduction in either fibre type. In conscious guinea-pigs [D-Pro2,D-Trp7,9]SP injected adjacent to the sciatic nerve was found to block motor but not sensory functions of the limb. Thus, commonly used tachykinin antagonists, but not SP itself, have potent local anaesthetic properties. This should be considered when these agents are employed as pharmacological tools.
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PMID:Tachykinin antagonists have potent local anaesthetic actions. 241 79

Anterograde axonal transport of substance P-like immunoreactivity (SPLI) decreases after injury (crush or resection) to rat sciatic nerve. If the axons regenerate a partial recovery of transport occurs. If regeneration is impeded the decrease in transport is more severe and prolonged. No changes in the proportion of mobile SPLI (31%) or transport velocity (10.0 mm/h) occur. The decrease in SPLI transport largely accounts for the decline in SPLI content which occurs in nerve following injury and probably reflects decreased cell body synthesis.
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PMID:Axonal transport of substance P-like immunoreactivity in regenerating rat sciatic nerve. 241 64

The occurrence of tachykinins in sensory neurons of the guinea-pig was studied by means of radioimmunoassay combined with ion-exchange and high-performance liquid chromatography as well as by immunohistochemistry. Antisera raised against kassinin (antiserum K12), neurokinin A (NKA) (antiserum NKA2) and substance P (SP) (antisera SP25 and SP2) were used. Antiserum K12 detected NKA, neuropeptide K (NPK) and a component eluting in the position of eledoisin (ELE) in extracts of the lung and ureter. Neurokinin B (NKB) was, however, not found. Neutral water extraction favored recovery of NKA and of the ELE-like component, while NPK was found only in acid extracts. The SP antisera detected two immunoreactive components of which the major form coeluted with synthetic SP. Capsaicin pretreatment depleted all these various forms of immunoreactivity in several peripheral organs including the ureter and lung. The immunoreactivity detected by antisera K12 or SP25 in radioimmunoassay had a similar regional distribution pattern in peripheral tissues. Immunohistochemical examination revealed that antiserum NKA2 stained the same spinal ganglion cells as the SP2 antiserum. The distribution of capsaicin-sensitive nerve fibers stained by these two antisera was also identical in peripheral organs such as the ureter, inferior mesenteric ganglion, heart and lung. It is concluded that multiple tachykinins, including SP, NKA, NPK and an ELE-like peptide, are present in capsaicin-sensitive sensory nerves in the guinea-pig. This finding can most likely be related to the origin of SP, NKA and NPK from the same precursor molecule, subsequent posttranslational tissue processing and axonal transport to terminal regions.
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PMID:Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. 241 71

The axonal transport of substance P-hydrolyzing peptidase was studied both 2 and 10 days after the ligation of rat sciatic nerves. A peptidase(s) hydrolyzing substance P at the bonds of Phe7-Phe8 and Phe8-Gly9 was found to have accumulated to about 2 times the normal amount in the proximal segment 10 days after ligation. This enzyme activity was inhibited by ethylenediamine tetraacetate or dithiothreitol. These results suggest that this is a metalloendopeptidase which is slowly transported to inactivate neuropeptides in the nerve terminals.
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PMID:Axonal transport of substance P-hydrolyzing peptidase in rat sciatic nerves. 242 11

In this study we tried to establish by the electron microscopic 'mirror technique' whether substance P-like immunoreactive neurons in the neostriatum receive synaptic inputs from catecholaminergic, presumably dopaminergic, nigrostriatal axons. Tyrosine hydroxylase-immunoreactive (TH-IR) axonal boutons were in synaptic contact with the somas and proximal dendrites of SP-IR neostriatal neurons, which are medium in size and have unindented nuclei. This suggests that nigrostriatal dopaminergic neurons monosynaptically influence the strionigral substance P neurons.
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PMID:Innervation of substance P neurons by catecholaminergic terminals in the neostriatum. 242 66


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