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)

Neurotropin, a nonprotein component extracted from the skin of rabbits treated with vaccinia virus, has been clinically and experimentally reported to demonstrate analgesic effects. In this study, we investigated the antinociceptive action of neurotropin in relation to the serotonergic system, a pain inhibitory system, and substance P, a pain transmitter; we also attempted to determine whether it acts at the spinal or supraspinal level in mice. 1) The spinal cord (T6-T10) transection completely abolished the antinociceptive action of neurotropin, attenuated that of morphine, and had no influence on the action of clonidine. 2) The intrathecal substance P-induced behavior was inhibited by [D-Pro2, D-Trp7,9]-substance P, but not by neurotropin. 3) Preadministration of p-chlorophenylalanine or cyproheptadine inhibited the antinociceptive action of neurotropin. These data suggest that neurotropin does not directly act on pain transmitters at the spinal cord level, but acts at the supraspinal level, resulting in an inhibition of pain transmitter release at the spinal level by mediating pain inhibitory systems such as the serotonergic system in addition to the noradrenergic and GABAergic systems previously reported.
 ...
PMID:Analgesic mechanism of neurotropin: relation to the serotonergic system and influence of spinal cord transection. 248 Apr 65

Immunofluorescence histochemistry was used to determine the distribution of substance P, somatostatin and cholecystokinin-octapeptide-immunoreactive perikarya in C6, T6, T10, L2 and S1 dorsal root ganglia of rat. Five different categories of immunoreactive primary afferent neurons were distinguished on the basis of cell size, cytology and peptide immunoreactivities. The population of small cells (diameter less than 20 microns) included three groups which were identified as containing somatostatin, substance P, or substance P + cholecystokinin-octapeptide. Two groups of cells were identified in an intermediate size range (diameter 21-43 microns) as containing cholecystokinin-octapeptide or cholecystokinin-octapeptide + substance P. These categories may reflect four distinct populations of primary afferent neurons. The relative abundance of dorsal root ganglion cells containing substance P, cholecystokinin-octapeptide or somatostatin immunoreactivities was significantly different within segmental levels. More neurons were immunoreactive for cholecystokinin-octapeptide than substance P in ganglia C6, T6 and T10. Somatostatin-containing cells were fewest in number regardless of level. The number of immunoreactive cells also varied among spinal ganglia. L2 contained the greatest number of immunoreactive cells; S1 contained the fewest. These studies are relevant to our understanding of dorsal root ganglia in two ways. Firstly, the data document significant variation in the distribution of peptide-containing neurons among spinal ganglia associated with various cord levels. The variation in peptide-containing cell populations among spinal ganglia may reflect differences in populations of modality-specific primary afferent fibers as well as in populations of somatic and visceral primary afferent fibers at each level. Furthermore, the data indicate that the relative abundance of a population of peptide-containing primary afferent neurons cannot be extrapolated from the examination of spinal ganglia from a single level. Secondly, substance P and cholecystokinin-octapeptide did not co-exist in all spinal ganglion cells as previously reported. In conjunction with immunostaining characteristics and cell size, the differential distribution of the two peptides defined four cell types, raising the possibility that each cell type may mediate a different modality.
 ...
PMID:Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat. 258 Nov 69

In urethane-anaesthetized rats, the intrathecal administration of 6.5 nmol of substance P (SP), neurokinin A (NKA), or neurokinin B (NKB) at the T8-T10 level of the spinal cord enhances mean arterial pressure and heart rate. However, in the pentobarbital-anaesthetized rat, while NKB produces no effect on mean arterial pressure, NKA produces a biphasic change and SP, a depressor response. All three neurokinins elicit a tachycardia. The following rank order of potency SP greater than or equal to NKA greater than NKB is observed in relation to these cardiovascular responses when either one of the two anaesthetics is used. The low cardiovascular activity of NKB cannot be attributed to its hydrophobicity, as the water soluble analogue of NKB, [Arg0]NKB, elicits a response as weak as the native peptide. In pentobarbital-anaesthetized rats, the intrathecal administration of 6.5 nmol of SP, also enhances plasma protein extravasation in cutaneous tissues of the back, the hind paws, and the ears. In this response NKA and NKB are either inactive (skin of hind paws) or less potent than SP (ears and dorsal skin). These findings agree with the hypothesis that in the rat spinal cord, the neurokinin receptor producing changes in mean arterial pressure, heart rate, and vascular permeability is of the NK-1 subtype.
 ...
PMID:Spinal action of neurokinins in the rat: effects on mean arterial pressure, heart rate, and vascular permeability. 283 32

1. The afferent innervation of the distal ileum has been examined in normal rats and in rats treated at birth with capsaicin. Electrophysiological recordings were made using an in vitro preparation of distal ileum and its associated mesenteric nerves. The fibre composition of the mesenteric nerves was examined by electron microscopy and the numbers of primary afferent fibres innervating a segment of distal ileum was estimated using retrograde tracing. 2. Recordings were made from 120 single afferent units all of which showed some degree of background activity. The conduction velocities of sixty-seven afferent units were estimated, and all were found to be in the C-fibre range (less than 2 m/s). Eighty-two units were sufficiently studied to allow their classification according to whether they responded to mechanical stimuli (M units), chemical stimuli (Ch units) or both mechanical and chemical stimuli (MCh units). In control rats 85.5% were classified as MCh units, 11.9% as M units and 2.6% as Ch units. In capsaicin-treated rats six single and three multi-units were MCh and one multi-unit was classified as an M recording. 3. The effects of intraluminal distension were investigated in sixty-seven units which were classified according to whether or not they adapted during the distension. About half the total units were classified as rapidly adapting, the other half were slowly adapting. This distribution was similar for the MCh-units, but of the eight M units tested, seven adapted during distension. The distension thresholds were tested in thirty units, of which twenty-eight responded at thresholds below 18 mmHg. There were no differences in the thresholds of units from control and capsaicin-treated rats. 4. The chemosensitivity of units was tested in response to acetylcholine (ACh), bradykinin and substance P. Most units tested responded to ACh (78% of MCh units tested) and bradykinin (80% of MCh units), but fewer units responded to substance P (about 50% of MCh units). ACh produced an increased tension which outlasted the increase in afferent activity. Bradykinin gave long-lasting afferent responses which were not always accompanied by increases in tension. The increases in afferent activity produced by substance P were often seen after an increase in tension. 5. The fluorescent dye True Blue injected into the wall of the ileum labelled cell bodies in the spinal and nodose ganglia, predominantly on the left side of an animal. The mean number of labelled cells per animal was eighty-seven, of which the majority was in the T10-T13 spinal ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:An electrophysiological and anatomical study of intestinal afferent fibres in the rat. 317 91

Renal afferent neurons were retrogradely labeled with FluoroGold in Sprague-Dawley rats at 50, 60, 70, 80, 90, 110, 130 and 200 days of age. Recordings of afferent renal nerve activity (ARNA) and immunofluorescent assessment of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and substance P (SP)-LI in spinal ganglia T10-L1 were obtained in the same rats. The frequency of renal afferent neurons positive for CGRP-LI declined abruptly from 88% in animals younger than 100 days of age (342 of 388 total cells) to 63% in rats older than 100 days of age (223 of the 353 total cells). The intensity of CGRP-LI (scaled 1-3) in renal afferent CGRP-positive neurons also declined significantly from a mean of 2.23 +/- 0.04 before 100 days to 1.48 +/- 0.05 in older rats (P < 0.001 in each age group). SP-LI positive neurons declined from 44% to 28% (P < 0.001). These changes in neuropeptide immunofluorescence coincided with an altered pattern of ARNA in which the excitatory response to complete renal ischemia increased from 274 +/- 69% above background to 1167 +/- 124% after the age of 100 days. Previous studies have shown that this alteration in the ARNA response to renal ischemia is due to the appearance of activity from R1 chemoreceptor nerves in ARNA. These data demonstrated that this transition in the electrophysiologic characteristics of ARNA is accompanied by profound alterations in CGRP-LI and SP-LI levels in renal afferent nerve cell bodies.
 ...
PMID:Age-related changes in calcitonin gene-related peptide and substance P in renal afferent nerve soma in the rat. Association with afferent renal nerve activity. 899 10

Dorsal column stimulation (DCS) is used clinically to provide pain relief from peripheral vascular disease and has the benefit of increasing cutaneous blood flow to the affected lower extremities. The purpose of this study was to examine the role of dorsal roots, calcitonin gene-related peptide (CGRP), and substance P in the cutaneous vasodilation induced by DCS. Male rats were anesthetized with pentobarbital sodium (60 mg/kg ip). A unipolar ball electrode was placed unilaterally on the spinal cord at the L1-L2 spinal segment. Blood flow was recorded in each hindpaw foot pad with laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS (either 0.2 mA subdural or 0.6 mA epidural at 50 Hz, 0.2-ms pulse duration). Dorsal rhizotomy of L3-L5 (n = 5) abolished the cutaneous vasodilation to subdural DCS, whereas removal of T10-T12 (n = 5) and T13-L2 dorsal roots (n = 5) did not attenuate the DCS-induced vasodilation. The CGRP antagonist, CGRP-(8-37) (2.6 mg/kg iv, n = 7), eliminated the epidural DCS-induced vasodilation, whereas the substance P receptor antagonist, CP-96345 (1 mg/kg iv, n = 6), had no effect. In summary, L3-L5 dorsal roots and CGRP are essential for the DCS-induced vasodilation. We propose that DCS antidromically activates afferent fibers in the dorsal roots, thus causing peripheral release of CGRP, which produces cutaneous vasodilation.
 ...
PMID:Cutaneous vasodilation during dorsal column stimulation is mediated by dorsal roots and CGRP. 912 59

The influence of the new antioxidant compound H-290/51 was examined on the substance P endopeptidase (SPE) activity in a rat model of spinal cord injury. This compound (H-290/51) has neuro-protective effects on edema and cell changes in this model. Infliction of trauma to the cord by making an incision into the right dorsal horn of the T10-11 segment resulted in a marked upregulation of SPE in the segments rostral to the lesion. On the other hand, the injured and adjacent caudal segments exhibited a marked down-regulation of the enzyme activity. Pretreatment with H 290/51 increased the SPE activity in the T9 segment but downregulated the enzyme activity in the T10-11 and T12 segments. The drug induced enzyme activity change was not further influenced by the trauma of the cord. The results indicate that a focal trauma induces widespread alterations in spinal cord SPE activity which can be influenced by the anti-oxidant drug H 290/51, suggesting that SPE is somehow involved in cell injury.
 ...
PMID:Substance P endopeptidase activity in the rat spinal cord following injury: influence of the new anti-oxidant compound H 290/51. 941 25

This study was undertaken to determine the segmental organization of the dorsal root ganglion (DRG) cells that give rise to pancreatic afferents containing a certain neuropeptide in the rat. These cells were examined using retrograde tracing combined with immunohistochemistry. Injection of horseradish peroxidase (HRP) into the pancreas resulted in the labeling of cells in bilateral T5-L2 DRGs, with most labeled cells lying at T10-T11. Injection into the duodenal (right), splenic (left), and entire lobes consistently produced more labeled cells significantly in the right, left, and right DRGs, respectively. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, somatostatin (SOM)-, and galanin (GAL)-immunoreactive (IR) cells in the DRGs (T9-T12) were found in -52, 17, 8, and 6%, respectively, but neuropeptide Y- and vasoactive intestinal polypeptide-IR cells were not found. About 88% of HRP-labeled cells in DRGs (T9-T12) contained CGRP, and approximately 16% of them contained SP. Although SOM- and GAL-IR cells were localized in the DRGs, these cells innervating the pancreas could not be found. In brief, these results show that bilateral (not similar in cell number on each side) DRG cells innervate the duodenal or splenic pancreas, and the majority of these cells that project to the pancreas contain CGRP and SP.
 ...
PMID:Afferent innervation of the rat pancreas: retrograde tracing and immunohistochemistry in the dorsal root ganglia. 943 67

The functional structure of the cat stellate ganglion (SG) and, in particular, its extra- and intraganglionic connections and neuronal organization, were investigated using histochemical, immunohistochemical, morphological and histological methods. Retrograde axonal transport of horseradish peroxidase was used to determine most of the extraganglionic interactions. Of the targets tested, the most extensive efferent connections of the SG were with the stemocleidomastoid muscle, trachea, esophagus and heart. Neurons of the SG also send a small number of postganglionic efferents to the thyroid and stomach. Furthermore, ganglion cells send axons to the spinal ganglia. Several afferent connections of the SG were determined. Sympathetic preganglionic neurons of segments C8-T10 of the spinal cord, sensory neurons of C8-T9 spinal ganglia, intramural ganglia of the thoracic viscera and the reticular formation of the medulla oblongata send their axons to the SG. Intraganglionic interactions of intemeurons with principal ganglionic cells were assumed to occur, based on the presence of interneurons immunoreactive to GABA and substance P. GABA- and substance P-immunoreactive fibers located around a small number of postganglionic neurons were also identified. Morphological study revealed asymmetry between the left and right ganglia: the right ganglion is larger than the left and contains more cells. This asymmetry was also reflected in basic structural parameters of neurons, such as average neuronal area and average diameter of cell somata. The present data has been used to develop a scheme for the basic inter- and intraneuronal connections of the cat SG. This ganglion is a true nervous center, with postganglionic neurons, some of which might be performing sensory functions, and interneurons. The ganglion is connected not only with the spinal cord and spinal ganglia, but also with neurons of the intramural ganglia and, by direct links, with efferent neurons of the medulla oblongata. Thus, the SG may play an essential role in viscera-visceral reflexes.
 ...
PMID:Neuronal organization and cell interactions of the cat stellate ganglion. 1187 85

Although pain is a cardinal feature of pancreatitis, its pathogenesis is poorly understood and treatment remains difficult. Nociceptive sensitization in several somatic pain models has been associated with activation of protein kinases including trkA, protein kinase C, and protein kinase A. We therefore tested the hypothesis that systemic treatment with a kinase inhibitor, k252a, known to inhibit all of these kinases would alleviate pain in an animal model of pancreatitis. Von Frey filament testing of somatic referral regions was evaluated as a method to measure referred pain in a rat model of acute necrotizing pancreatitis induced by L-arginine. Rats with pancreatitis showed increased sensitivity to abdominal stimulation with Von Frey filament. This referred mechanical sensitivity was associated with an 8-fold increase in levels of phosphorylated trkA in the pancreas and with significant up-regulation of both calcitonin gene-related peptide and preprotachykinin mRNA expression in thoracic dorsal root ganglia and with increased calcitonin gene-related peptide and substance P immunoreactivity in spinal cord segment T10. Treatment with the kinase inhibitor k252a suppressed the phosphorylation of trkA in the pancreas as well as reversed both the behavioral changes and the increase in neuropeptide expression associated with pancreatitis.
 ...
PMID:Acute pancreatitis results in referred mechanical hypersensitivity and neuropeptide up-regulation that can be suppressed by the protein kinase inhibitor k252a. 1462 90


<< Previous 1 2 3 Next >>