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)

Ulex europaeus agglutinin I (UEA-I) is a plant lectin with an affinity for L-fucosyl residues in the chains of lactoseries oligosaccharides associated with medium- and smaller-diameter dorsal root ganglion neurons and their axonal processes. These enter Lissauer's tract and terminate within the superficial laminae of the spinal cord overlapping projections known to have a nociceptive function. This implies that the surface coatings of neuronal membranes may have a relationship with functional modalities. The present investigation further examined this concept by studying a neuronal projection with a nociceptive function to determine whether fucosyl-lactoseries residues were incorporated in its primary afferent terminals. Transganglionic transport of horseradish peroxidase (HRP) following injection into tooth pulp chambers was employed to demonstrate dental pulp terminals in the trigeminal spinal complex, while peroxidase and fluorescent tags were used concomitantly to stain for UEA-I. Double immunolabeling for substance P (SP) and gamma-aminobutyric acid (GABA) using peroxidase and colloidal gold allowed a comparison of the distribution of a known excitatory nociceptive transmitter with that of UEA-I binding in specific subnuclei. Synaptic interrelationships between UEA-I positive dental pulp primary afferent inputs and specific inhibitory terminals were also examined. SP immunoreactivity occurred in laminae I and outer lamina II (IIo) of subnucleus caudalis (Vc) and in the ventrolateral and lateral marginal region of the caudal half of subnucleus interpolaris (Vi), including the periobex area in which Vi is slightly overlapped on its lateral aspect by cellular elements of Vc. The adjacent interstitial nucleus (IN) also showed an intense immunoreactivity for this peptide antibody. UEA-I binding displayed a similar distribution pattern in both Vc and Vi, but extended into lamina IIi and the superficial part of Lamina III in Vc. Dental pulp terminals were found to have a comparable distribution; however, many extended into the dorsal portion of the caudal half of Vi and the ventromedial quadrant of rostral Vi. Electron-microscopic analysis showed that transganglionically labeled dental pulp terminals contained ovoid, complex membrane-bound vacuoles laden with transported HRP. The preterminal axon and synaptic membranes of those dental pulp terminals located in zones of Vc and Vi displaying an affinity for UEA-I were usually characterized by a patchy, electron-dense coating of the peroxidase tag. SP was demonstrated ultrastructurally with Protein-A colloidal gold (3-nm particles), whereas GABA immunoreactivity was revealed by the avidin-biotin-peroxidase method.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ulex europaeus agglutinin-I binding to dental primary afferent projections in the spinal trigeminal complex combined with double immunolabeling of substance P and GABA elements using peroxidase and colloidal gold. 247 97

Several immunogold techniques were used to determine the ultrastructural localization of calcitonin gene-related peptide (CGRP), tachykinin, somatostatin, and gamma-amino-butyric acid (GABA) immunoreactivity in the dorsal horn of rat spinal cord. The immunocytochemical reactions were carried out directly on ultrathin sections from non-osmicated frozen tissue, non-osmicated low temperature-embedded (Lowicryl K4M) tissue, and osmicated epoxy-embedded material. Preservation of ultrastructural morphology and immuno-labeling efficiency were compared. Morphology of subcellular organelles was relatively good in ultra-thin frozen sections, which showed the highest immunoreactivity. However, only very small samples of tissue could be examined. Although there was relatively good immunolabeling in the Lowicryl K4M-embedded tissue, the ultrastructure of the neuropil, and particularly that of synapses, was poorly maintained. In contrast, the osmicated epoxy-embedded material offered optimal morphological preservation together with accurate subcellular localization of all antigens under study. The latter approach thus enabled clear visualization of CGRP, tachykinin, and somatostatin immunoreactivity restricted to large dense-cored vesicles (90-150 nm diameter) in many axonal and synaptic profiles in the superficial layers of the dorsal horn. CGRP- and tachykinin-positive profiles were also present in the tract of Lissauer. GABA immunoreactivity was present mainly in axons and terminals, and less frequently in somatic and dendritic profiles. In terminals, which often formed symmetrical synapses on immunonegative dendritic profiles, it was associated with small (30-60 nm diameter) clear vesicles and mitochondria. Double immunolabeling was possible on all preparations, but the osmicated, epoxy-embedded material clearly showed co-localization of peptides, especially of CGRP and tachykinins, within the same dense-cored vesicles in axonal fibers and/or terminals. On the other hand, peptide and GABA immunoreactivity were consistently seen in different nerve profiles. In a few cases, GABAnergic terminals were seen to synapse on tachykinin-positive fibers.
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PMID:Ultrastructural localization of neuropeptides and GABA in rat dorsal horn: a comparison of different immunogold labeling techniques. 256 4

The light microscopic morphology and distribution of non-substance P-containing small primary afferent fibres were studied. These fibres were labelled using LD2 and LA4 monoclonal antibodies which recognize alpha-galactose extended oligosaccharides expressed by primary afferent neurons. The LD2 and LA4 antibodies immunostained small primary afferent fibres ending mainly in lamina II of the spinal cord dorsal horn and trigeminal subnucleus caudalis of the rat. The lamination pattern of both types of primary afferents was assessed using an image analysis system. The highest density of LD2-immunoreactive fibres was located in a patchy band located in lamina II outer, while LA4-immunoreactive fibres were distributed mainly through lamina II inner. In lateral regions of cervical and lumbar dorsal horn the LA4-immunoreactive band is broader and comprises almost all lamina II. In contrast to substance P-containing primary afferents, a low density of LD2- or LA4-immunoreactive fibres was found in lamina I, and no terminal fields were found in lamina V or lamina X of the spinal cord or in levels of the trigeminal system outside the subnucleus caudalis. Both antibodies also labelled the parent fibres in the white matter fasciles. LD2-immunoreactive fibres were located in the dorsal roots, medial regions of the Lissauer tract, dorsal columns of the spinal cord, outer regions of the spinal trigeminal tract and dorsal to the cuneatus and gracilis nuclei. In contrast, LA4-immunoreactive fibres were restricted to the dorsal roots, medial and lateral regions of the Lissauer tract and the outer regions of the trigeminal tract. Immunostained fibres in the rootlets of the X and IX nerves and immunoreactive terminal arborizations in various subnuclei of the nucleus tractus solitarius were seen using both antibodies. These results show that subpopulations of small primary afferents stained by LD2 and LA4 antibodies have distinct patterns of central distribution and are consistent with a subdivision of small primary afferents into peptide- and non-peptide-containing groups.
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PMID:Morphology and distribution of primary afferent fibres expressing alpha-galactose extended oligosaccharides in the spinal cord and brainstem of the rat. Light microscopy. 261 81

The distribution of substance P-like (SPLI) and methionine-enkephalin-like (MELI) immunoreactivity in the thoracic, lumbar, and sacral human spinal cord was studied in sections stained by the indirect antibody peroxidase-antiperoxidase method. The laminar distributions of SPLI and MELI were somewhat similar. Immunoreactive axons and terminal-like processes were found in the marginal zone and substantia gelatinosa, although SPLI was heavier than MELI in Lissauer's tract and the marginal zone. Laterally, both SPLI and MELI extended along the entire dorsal horn border, including laminae IV and V. Isolated, fine fiber bundles also extended deep into the central regions of laminae IV and V. Heavy SPLI and MELI also were found in the intermediolateral column region (IML), while lesser amounts were observed in the intercalatus and intermediomedial (IMM) regions of lamina VII. In lamina IX, SPLI was moderate, and less MELI was found. The distribution of SPLI fibers and terminal-like profiles in the human spinal cord is similar to that in other mammals, whereas that of MELI suggests some differences, particularly in laminae I, II, and III. Many terminal-like structures were in close apposition to neurons in several laminae. Based upon correlations of the three-dimensional organization of both the labeled terminals and the dendritic trees of the cells, the types of neurons in apposition to SPLI and MELI could be tentatively identified. These may include (1) marginal cells resembling the pyramidal and multipolar types; (2) gelatinosal cells resembling islet and stalked cells; (3) spinothalamic cells in laminae I, V, VI, VII, and VIII; (4) autonomic neurons in the IML and IMM; and (5) motoneurons in lamina IX. In the sacral cord, neurons resembling dorsal band (lamina V) and lateral band (lamina VII) parasympathetic neurons also were outlined by SPLI and MELI, with more SPLI in the region of the lateral band neurons. Often, in many of the laminae, the same neuron was surrounded by both SPLI and MELI. The variety of possible neuronal types supplied by SPLI and MELI processes and the fairly wide distribution of these substances within the spinal cord suggest that they may be involved in a number of spinal functions.
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PMID:The human spinal cord: substance P and methionine-enkephalin immunoreactivity. 618 Dec 29

In the present study we have employed immunoperoxidase techniques to investigate the distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the spinal cord and sensory ganglia of the cat. The spinal distribution of VIP-containing neuronal processes was also compared with that of substance P (SP), somatostatin (SOM), and cholecystokinin-8 (CCK) at lumbar, sacral, and coccygeal levels. At sacral levels, VIP was found to be contained in small and medium-sized primary sensory neurons and in dorsal rootlets. Deafferentation, by either ganglionectomy or dorsal rhizotomy, resulted in a nearly complete loss of VIP immunoreactivity in the spinal cord. The spinal distribution of VIP fibers and terminals was most dense and extensive in sacral segments. Forming a thin shell around the dorsal horn, collaterals, apparently originating from Lissauer's tract, projected either medially or laterally through lamina I. Laterally, many VIP axons terminated in lateral laminae V to VII. Others projected further through the neck of the dorsal horn to medial lamina V and the gray matter near the central canal. Medially, VIP axons descended through lamina I to expand into terminal fields in the posterior commissure and medial lamina V. At the ultrastructural level, VIP-like immunoreactivity was found in dense core vesicles within axonal enlargements containing both large dense core and smaller clear round vesicles. Synaptic connections were infrequently observed but, when encountered, were of the simple axodendritic type. The spinal distribution of VIP-containing fibers was remarkably similar to that reported for pelvic nerve visceral afferents, both in termination patterns within the spinal gray matter and in localization to the sacral cord. The density of SP-, SOM-, and CCK-containing fibers and terminals was constant at all levels examined (L4 to Co4). In marked contrast, the distribution of VIP fibers, much like that of pelvic nerve afferents, was mostly confined to sacral segments. Thus, although SP, SOM, and CCK may be contained within a population of sacral visceral afferents, they must be common to afferent systems in other segments as well. VIP, however, appears to be preferentially contained within pelvic visceral afferent fibers confined mostly to sacral segments.
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PMID:Preferential immunohistochemical localization of vasoactive intestinal polypeptide (VIP) in the sacral spinal cord of the cat: light and electron microscopic observations. 619 17

A gate control exists by which peripheral afferents and descending pathways can modulate sensory transmission. Evidence is presented that the mechanism may exist in the substantia gelatinosa laminae II and III. This area receives all known types of peripheral afferent from skin, from viscera and from high-threshold muscle afferents. The chemistry of the region is unique. Peripheral afferent terminals contain substance P, somatostatin, and fluoride-resistant acid phosphatase. Cells in the region contain enkephalin and GABA. At least three descending systems from the brainstem terminate in the area. The anatomical substrate exists by which cells in laminae II and III can receive afferents and descending axons and intrude onto cells of laminae I, IV, and V. Stimuli limited to the axons of laminae II and III cells in the Lissauer tract produce dorsal root potential and change the excitability of mono- and polysynaptic reflexes. They also change the excitability and receptive fields of cells in laminae IV and V. Recording from single units in laminae II and III reveals cells with many unusual properties not seen in the large dorsal horn cells. These unusual properties include small receptive fields, very prolonged responses to single stimuli, prolonged habituation, and shifting receptive fields. The action of the gate control shows it to be subtle and far beyond a simple control of overall excitability. Excitations and inhibitions are independently controlled. Different types of convergent afferent may be turned on and off. There are signs of both short-and long-lasting actions. It seems that a good case has been made for the cells of substantia gelatinosa taking part in the gate control mechanism.
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PMID:The role of substantia gelatinosa as a gate control. 624 35

Previous descriptions of immunoreactive vasoactive intestinal polypeptide (VIP) in small-diameter dorsal root ganglion cells in the superficial dorsal horn implicated this 28 amino acid peptide in nociceptive transmission. In this study, we examined the distribution of immunoreactive VIP in the spinal cord and caudal medulla of cats and rats. The PAP method was used on paraffin and frozen sections of 4% paraformaldehyde-fixed tissue, using antibodies to VIP that were raised in rabbits. The distribution of immunoreactive VIP, while similar to that of substance P (SP), a putative primary afferent peptide neurotransmitter, is more restricted. VIP staining is found in sacral dorsal roots and densely in the Lissauer tract. Dorsal horn staining is concentrated in lamina I. In contrast to SP, lamina II is almost devoid of staining. Labeled VIP axons course along the lateral curvature of the dorsal horn and arborize across lamina V and around the central canal. A collateral branch of these fibers distributes to the sacral autonomic nucleus. A few fibers could be traced from the root entry zone to the contralateral central gray. VIP axons also terminate between ependymal cells of the central canal. Unlike SP, immunoreactive VIP was restricted, almost exclusively, to the sacral cord. The few fibers in the lumbar enlargement and in the coccygeal cord apparently derive from ascending and descending sacral primary afferents. In fact, the VIP pattern is almost identical to that reported for afferents from the pelvic viscera, including a discontinuous rostrocaudal distribution. Since the staining pattern is also very similar to that of A-delta high-threshold mechanoreceptors, the possibility is discussed that whereas VIP is not a general "somatic" primary afferent transmitter, it may transmit nociceptive input from the pelvic viscera.
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PMID:Immunoreactive vasoactive intestinal polypeptide is concentrated in the sacral spinal cord: a possible marker for pelvic visceral afferent fibers. 667 14

Secretoneurin is a peptide of 33 amino acids generated in brain by proteolytic processing of secretogranin II. The distribution of this newly characterized peptide was investigated by means of immunocytochemistry and in situ hybridization in the spinal cord and lower brainstem of the rat. The staining pattern of secretoneurin immunoreactivity (IR) was compared to that of substance P (SP) and calcitonin gene-related peptide (CGRP) in adjacent sections. A high density of secretoneurin-IR fibers and terminals was found in lamina I and outer lamina II of the caudal trigeminal nucleus and of the spinal cord at all levels, around the central canal, and in the sympathetic and parasympathetic areas of the lateral cell columns. The ventral horn displayed a low to moderate density of secretoneurin-IR. The highest number of secretogranin II mRNA-containing cells was found in lamina II of the dorsal horn and in neurons of the dorsal root ganglia. In the white matter, secretoneurin-IR was most prominent in the dorsolateral part of the lateral funiculus and in the tract of Lissauer. The distributions of secretoneurin-IR and SP-IR were strikingly similar. CGRP-IR and secretoneurin-IR overlapped in the outer laminae of the dorsal horn, in the lateral cell column, and probably in some motoneurons. This study establishes that, like SP and CGRP, secretoneurin is a peptide highly concentrated in the terminal field of primary afferents and in sympathetic and parasympathetic areas. Thus secretoneurin might be involved in the modulation of afferent transmission.
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PMID:Distribution of secretoneurin immunoreactivity in the spinal cord and lower brainstem in comparison with that of substance P and calcitonin gene-related peptide. 751 98

In this study we have described the ontogeny of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the sacral spin cord, of fetal sheep (n = 37) from 56 to 140 days of gestation (term = 146 days). A few fine, varicose fibres immunoreactive for calcitonin gene-related peptide were present in Lissauer's tract, the dorsolateral funiculus and in laminae I and V in the dorsal horn of the spinal cord at 56-61 days of gestation. At this age, two groups of intensely staining immunoreactive cells were present in the motoneuron pool in laminae VIII and IX in the ventral horn of the spinal cord. By 77 days, immunoreactive fibres were also present in laminae II and X. With advancing gestational age, an increase in the intensity of staining was observed throughout the cord to term, with the exception of laminae VIII and IX, where a decrease was seen. Intense staining of cells in the motoneuron pool was evident until c. 128 days, after which time staining became very faint. Fine fibers immunoreactive for substance P were present in Lissauer's tract and lamina I of the spinal cord at 56-61 days of gestation. They were also present throughout laminae IV-VI and X as well as throughout the entire ventral horn. Immunoreactive fibres in lamina II were evident by 77 days. The staining increased in density but remained similar in distribution with increasing gestational age to term in the dorsal horn, but decreased markedly in the ventral horn. Cells immunoreactive for substance P were evident from 56 days, particularly on the border of laminae II and III, until late in gestation. Ultrastructural studies showed that axon terminals immunoreactive for calcitonin gene-related peptide and for substance P were present in lamina I by 61 days. Immunoreactivity for glutamate was evident at 83 days in dorsal root fibers and also in lamina I and II, where it was more prominent in cells than in fibres. At all ages examined, the dorsal horn stained more intensely than the ventral horn. Immunoreactivity for glutamate and neuropeptides appeared in the cells and fibres of dorsal root ganglia at 97-100 days. In the skin, immunoreactivity for calcitonin gene-related peptide and substance P was present at 85 days, some time after its appearance in the cord. Fibres immunoreactive for serotonin appeared in lamina I, at the neck of the dorsal horn and in the ventral horn at 83 days of gestation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Development of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the spinal cord of fetal sheep. 768 61

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


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