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)

The lectin soybean agglutinin (SBA) from Glycine max binds to small-sized dorsal root ganglion cells and their central terminals in the superficial dorsal horn of the spinal cord. Here we investigated the ability of SBA and SBA conjugated to horseradish peroxidase (SBA-HRP) to trace thin calibre afferents into the spinal cord from a peripheral nerve. Following injection into the sciatic nerve, labelled cells in the dorsal root ganglion were predominantly small-sized but some medium-sized cells were also labelled. Colocalization studies of transported SBA with various neuronal markers showed that all neurons that transported SBA-HRP showed SBA binding, indicating high uptake specificity for the conjugate. 15% were immunoreactive for RT97 indicating that some axons were myelinated, and 54% also expressed binding sites for isolectin B4 from Griffonia simplicifolia, a selective marker for a subpopulation of unmyelinated afferents. With regard to neurotransmitter content, 43% of the SBA cells contained calcitonin gene-related peptide, 33% contained substance P and 2.5% somatostatin. In addition, 3% contained carbonic anhydrase. Centrally, injection of SBA in the sciatic nerve resulted in labelled terminals in somatotopically appropriate regions of laminae I-II of the dorsal horn, and in the gracile nucleus. A few neurons in the dorsal horn were labelled indicating that some transneuronal transport of SBA had occurred. The results show that SBA can be used as a transganglionic tracer to label fine calibre primary afferents that project to laminae I-II of the spinal cord and the gracile nucleus. It appears to label more afferents than isolectin B4, including also a subpopulation of myelinated afferents.
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PMID:Transganglionic transport of the lectin soybean agglutinin (Glycine max) following injection into the sciatic nerve of the adult rat. 1064 Jan 82

The type of trigeminal ganglion cells that express 5-HT1B receptors has not been well characterized, despite the fact that these receptors are important targets for anti-migraine drugs. We have therefore used combined in situ hybridization and immunofluorescence to examine the expression of 5-HT1B receptor messenger RNA in identified subpopulations of rat trigeminal ganglion cells. 5-HT1B-expressing cells accounted for 15% of all trigeminal ganglion cells, were medium sized, and showed immunoreactivity for either 200,000 mol. wt neurofilament, calcitonin gene-related peptide, or nerve growth factor receptor (trkA). In contrast few 5-HT1B cells showed immunoreactivity for substance P or binding of the lectin Griffonia simplicifolia IB4. Our results are consistent with 5-HT1B receptors acting to control the release of calcitonin gene-related peptide from trigeminal neurons with finely myelinated axons. 5-HT1B receptor agonists may reduce neurogenic vasodilation by activating such receptors. However many nociceptive trigeminal neurons, including the substance P and IB4-binding populations, do not express the 5-HT1B receptor.
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PMID:Expression of the 5-HT1B receptor by subtypes of rat trigeminal ganglion cells. 1065 26

A new sea urchin lectin from Toxopneustes pileolus, is D(+)galactose (Gal)-, D(+)fucose (Fuc)-specific. Incubation of rat peritoneal mast cells with the lectin in the presence of 0.3 mM CaCl2 for 10 min significantly and dose-dependently inhibited the histamine release induced by N-acetyl glucosamine (GlcNAc)-specific Datura stramonium agglutinin (DSA), an activator of the Gi-protein-dependent pathway in mast cells. This inhibition by the sea urchin lectin was sugar-specifically reversed in the presence of D(+)Gal or D(+)Fuc but not L(-)Fuc. The sea urchin lectin had no effect on the histamine release induced by compound 48/80, slightly inhibited the histamine release induced by substance P and mastoparan, and slightly enhanced the histamine release induced by melittin, but these effects were not dose-dependent. Compound 48/80, substance P, mastoparan and melittin are mast cell activators without sugar residues. It is suggested that the lectin binds to D(+)Gal residues of DSA to interfere with mast cell activation induced by DSA, a glycoprotein with arabinose and Gal residues. The effects of plant lectins with affinity to D(+)Gal, N-acetyl galactosamine and/or sialic acid and L(-)Fuc on the histamine release induced by DSA, compound 48/80 and substance P were also examined.
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PMID:D-galactose-specific sea urchin lectin sugar-specifically inhibited histamine release induced by datura stramonium agglutinin: differences between sugar-specific effects of sea urchin lectin and those of D-galactose- or L-fucose-specific plant lectins. 1138 49

Previous studies have found changes in neuropeptide expression in trigeminal ganglion cells after inferior alveolar nerve (IAN) section. These changes may play a part in the persistent sensory abnormalities that can be experienced after trigeminal nerve injuries. Here, neuropeptide expression after IAN ligation was studied, as this type of injury is thought to be more likely to result in sensory disturbances. The neuropeptides investigated were substance P, calcitonin gene-related peptide, enkephalin (ENK), galanin (GAL), neuropeptide Y (NPY) and vasoactive intestinal polypeptide. In anaesthetised adult female ferrets the left IAN was sectioned and the central stump tightly ligated. Recovery was allowed for 3 days, 3 or 12 weeks before perfusion-fixation. In a second procedure, 1 week before perfusion, the IAN was exposed and an injection made central to the injury site, using a mixture of 4% Fluorogold and 4% Isolectin B4 conjugated to horseradish peroxidase, to identify cell bodies with axons in the inferior alveolar nerve and cells with unmyelinated axons within this population, respectively. Control experiments involved tracer injection alone. After harvesting the tissue, sagittal sections were taken from both the right and left ganglia and immunohistochemical staining used to reveal the presence of peptides and Isolectin B4 tracer. The results showed a significant decrease in GAL expression after injury and an increase in ENK and NPY expression. No significant differences were seen in the expression of the other peptides or in the proportion of lectin-positive cells at any time after injury. When compared with previous data, significant differences were found between peptide expression following nerve ligation and nerve section. These results reveal that the changes in neuropeptide expression in the trigeminal ganglion that follow IAN injury are dependent upon the type of injury. The extent to which changes in the central neuropeptide levels contribute to the development of sensory disorders remains to be established.
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PMID:Neuropeptide expression in the ferret trigeminal ganglion following ligation of the inferior alveolar nerve. 1138 65

The time course and specificity of neuron addition to lumbar dorsal root ganglia (DRGs) L(4)-L(6) of rats was investigated. By using methods validated by three-dimensional reconstructions, profile counts in paraffin sections of nucleoli within a nucleus were 36% greater in 100-day-old (P100) rats than in 1-day-old (P1) rats. Adult values were reached by P50. Added neurons fell disproportionately into the population of neurons whose size was below that of the mean size within the ganglion. The biochemical characteristics of small neurons were used to determine whether added neurons fall into particular subpopulations. In DRGs, L(3) and L(4), the number of neurons immunoreactive to substance P (SP) or calcitonin-gene-related peptide (CGRP) or that bound the lectin isolectin B4 (IB4) was determined. Between P5 and P100, the number of SP-stained neurons increased by 2,280 (40% increase), CGRP-stained neurons increased by 6,080 (70% increase), and IB4-stained neurons increased by 6,900 (90% increase). The increase in the number of neurons stained for CGRP or IB4 was more than twice the number of neurons found to be added to these ganglia, indicating that coexpression of these markers as well as neuron number may be developmentally regulated during postnatal life.
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PMID:Sensory neuron addition in juvenile rat: time course and specificity. 1211 86

This study sought to explore the anatomical relationships between peptidergic nerves and blood vessels within human primary and permanent teeth. Extracted primary and permanent molars (n = 120) were split longitudinally, placed in Zamboni's fixative and the coronal pulps were processed for indirect immunofluorescence. Ten-micrometre-thick serial frozen pulp sections were triple-labelled using combinations of the following antisera: (1) protein gene-product 9.5 (PGP 9.5), a general neuronal marker; (2) one of the neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) or neuropeptide Y (NPY); and (iii) the lectin Ulex europeus, a label for vascular endothelium. The mid-coronal pulp region was examined, using fluorescence microscopy, to determine the proportion of blood vessels showing a positive innervation (recorded when PGP 9.5-labelled nerves appeared to intersect the vessel wall). In addition, the percentage of these vascular-related nerves expressing each of the above neuropeptides was recorded. Overall, 20% of pulpal blood vessels appeared to have a positive innervation. In the main these were thick-walled arterioles. Capillaries, venules and lymphatics were mostly devoid of an associated innervation. Ninety-two per cent of vascular-related nerves expressed CGRP, 87% expressed SP, 15% expressed VIP and 80% expressed NPY. There were no significant differences in overall innervation or peptide-related innervation between primary and permanent teeth (P < 0.05, ANOVA), indicating that pulpal blood flow is likely to be subject to similar neurological control mechanisms in both dentitions.
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PMID:Immunocytochemical investigation of neurovascular relationships in human tooth pulp. 1264 69

Substance P and neurokinin A (NKA) have potent pro-inflammatory effects in the airways. The release of these neuropeptides from primary afferent (sensory) nerve endings to various stimuli is considered to be induced by activation of the capsaicin (vanilloid) receptor (VR1). In this study, retrograde neuronal tracing studies were combined with immunohistochemistry for VR1 and substance P to investigate the occurrence and distribution of substance P and VR1 receptor expression in mouse trigeminal neurons that were identified by retrograde labeling with Fast blue dye from the nasal mucosa. Fast blue signaling was observed in mucosa layers of the right nasal cavity and in sensory trigeminal neurons close to the division of the ophthalmic and maxillary nerve. Expression patterns of VR1 and substance P were found with different frequencies: 11.3+/-1.2% (mean+/-SEM) were immunoreactive for VR1, 4.9+/-1.1% for VR1 and SP, and 6.4+/-1.3% only for VR1 but not for SP. These VR1-positive neurons were partly binding to lectin I-B4, indicating VR1-expression in non-peptidergic upper airway C-fibers. In conclusion, based on the extent of SP and VR1 co-localization in nasal afferent neurons, the present study suggests that, following a peripheral activation of the VR1 receptor on SP afferents, there could be a triggering of SP-mediated phenomena, including those related to inflammation, such as plasma extravasation.
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PMID:Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa. 1290 43

African naked mole-rats are subterranean rodents that have a robust orienting response to stimulation of unique vibrissa-like body hairs that are widely spaced over an otherwise hairless skin. To determine whether these large body hairs have a specialized organization similar to facial vibrissae, the structure and innervation of facial vibrissa follicles, body hair follicles, and intervening skin in naked mole-rats was compared with that in rats and a furred African mole-rat species (the common mole-rat). Immunofluorescence and lectin-binding analyses revealed that the body hair follicles in naked mole-rats were exceptionally large and well innervated, similar to guard hairs of furred species. However, these body vibrissae lacked the anatomic specializations and unique types of innervation affiliated with follicle sinus complexes of facial vibrissae. In contrast to the furred species, naked mole-rats had a paucity of Abeta-fiber Merkel endings at all peripheral locations. Naked mole-rats also were completely lacking in cutaneous C-fibers immunoreactive for substance P and calcitonin gene-related peptide. In contrast, the hairless skin of the naked mole-rats had an exceptional abundance of presumptive Adelta-fibers. The unusual features of the cutaneous innervation in naked mole-rats are presumably adaptations to their subterranean environment and that they are the only known poikilothermic mammal. The features of this mammalian model system provide unique opportunities to discriminate mechanisms related to tactile spatial orientation, vascular regulation, and nociception.
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PMID:Somatosensory organization and behavior in naked mole-rats: II. Peripheral structures, innervation, and selective lack of neuropeptides associated with thermoregulation and pain. 1292 19

Bradykinin (BK) has long been recognized as an important mediator of pain and inflammation. In normal tissue bradykinin causes an acute sensation of pain by an action at B2 receptors, but in inflamed tissue the pharmacology of the response changes to that of B1 receptors. Attempts to demonstrate the presence of functional B1 receptors in sensory neurones have failed, however, and the actions of B1 agonists have therefore been presumed to be indirect. Here we show that specific B1 receptor activation causes translocation of the epsilon isoform of protein kinase C (PKC-epsilon) to the membrane of a small fraction of freshly isolated sensory neurones from rats and mice. The proportion of neurones in which PKC-epsilon translocation was observed increased to around 20% of neurones after 3 days in culture with the neurotrophins glial cell line derived neurotrophic factor (GDNF) and neurturin, but not with nerve growth factor (NGF). Using in situ hybridization we found that the proportion of neurones expressing B1 mRNA increased from close to zero to 20.4% after 8 h culture in GDNF. Neurones expressing functional B1 receptors were negative for the neuropeptides CGRP and substance P, but most expressed functional TRPV1 receptors for capsaicin (60%) and bound the lectin IB4 (68%), both markers characteristic of nociceptors. B1 activation enhanced the heat-activated membrane current approximately 3-fold, and the enhancement was much more prolonged than was the case with B2 activation, consistent with a role for B1 receptors in sustained pain. We conclude that GDNF and neurturin potently upregulate functional B1 receptor expression in small non-peptidergic nociceptive neurones.
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PMID:Functional bradykinin B1 receptors are expressed in nociceptive neurones and are upregulated by the neurotrophin GDNF. 1531 21

The distribution and modulation of the P2X(3) receptor was studied in trigeminal ganglion neurons to provide insight into the role of ATP in craniofacial sensory mechanisms. Binding to the d-galactose specific lectin IB4 was found in 73% of P2X(3)-positive neurons while only 16% of IB4 neurons expressed P2X(3). Neurons expressing P2X(3) alone were significantly larger than IB4-or IB4/P2X(3)-positive neurons. Investigation of target-specificity revealed that 22% of trigeminal ganglion muscle afferent neurons were positive for P2X(3) versus 16% of cutaneous afferent neurons. Muscle P2X(3) afferents were significantly smaller than the overall muscle afferent population while P2X(3) cutaneous afferent neurons were not. Presumptive heteromeric (P2X(2/3)) muscle afferent neurons were also identified and comprised 77% of the P2X(3) muscle afferent population. Muscle afferent neurons co-expressed P2X(3) with either calcitonin gene-related peptide (15%) or substance P (4%). The number of P2X(3)-positive muscle afferent neurons significantly increased one and four days following complete Freund's adjuvant-induced masseter muscle inflammation, but significantly decreased after 12 days. These results indicate that within trigeminal ganglia: (1) the P2X(3) receptor is expressed in both small and medium-sized neurons; (2) the P2X(3) receptor is not exclusively expressed in IB4 neurons; (3) P2X(3) is co-expressed with neuropeptides; (4) differences in the proportion of cutaneous versus muscle P2X(3) afferents are not apparent. Trigeminal P2X(3) neurons therefore differ markedly from dorsal root ganglion P2X(3) afferents. This study also shows that deep tissue inflammation modulates expression of the P2X(3) receptor and thus may warrant exploration as a target for therapeutic intervention.
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PMID:Trigeminal P2X3 receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation. 1615 75


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