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 aim of this study was to describe the normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) containing fibres in the knee joint of the mouse and to obtain insight into the changes in innervation associated with degenerative processes in the joint. Arthrosis was induced by a single subpatellar intra-articular injection of bacterial collagenase. After decalcification in EDTA solutions, the CGRP and SP fibres were visualized by peroxidase-antiperoxidase pre-embedding immunocytochemistry for light microscopy. Control experiments on the mouse brain as a reference for the effect of EDTA on the immunostaining showed that the decalcification procedure with EDTA had not impaired the immunostaining. A rich innervation of thin varicose CGRP and SP immunoreactive fibres was found in most peri- and intra-articular tissue components. The periosteum, synovial tissues, the joint capsule and the intra-articular fat tissues were richly innervated. Less intense innervations were also found in the subchondral bone plates of the tibio-femoral joint and of the patella. Fibres were also found in the soft tissues between the patellar tendon and the femoral groove. No differences could be found between the location of CGRP and SP fibres with respect to the localization in the joint, but generally more CGRP fibres were found. The collagenase-induced osteoarthrosis was characterized by sclerosis of the subchondral bone, patellar dislocation, osteophyte formation, synovial proliferation and by severe cartilage abrasion, particularly on the medial side of the femoro-tibial joint. The overall distribution of CGRP and SP fibres was the same as in the control joints. However, major differences were found in all studied joints at specific locations around the cruciate ligaments, in the synovium around the patella, in the soft tissues lateral of the patella and in plica tissue between the patella and femoral groove. The CGRP and SP innervation was no longer detectable by immunolabelling with the antibodies. With a polyclonal antibody to the growth associated protein GAP-43/B-50, signs of degenerated axonal profiles were observed in these locations. At other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal. In conclusion, the present study provides detailed information on the localization of CGRP and SP fibres, which may be involved in pain perception. Knowledge of the changes that occur during arthrosis may give more insight into the clinical symptoms.
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PMID:Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse. 128 63

The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.
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PMID:Peptides in the gastrointestinal tract in human immunodeficiency virus infection. The GI/HIV Study Group of the University of Calgary. 153 25

In the mouse, arthritis was induced by a single sub-patellar intraarticular injection of bacterial collagenase. This procedure induces also patellar malalignment. A rich innervation of thin varicose calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactive fibers was found in the joint capsule, in the periosteum of the patella, in the synovial tissues at the lateral border of the patella, in the femoral groove, and in the subchondral bone of the patella and femur. Moreover, fibers were found in plica tissues between the quadriceps and patellar tendon, and the femoral groove. After the collagenase treatment, the general innervation pattern was comparable to that of the controls, but CGRP and SP innervation was no longer detectable with the antibodies in the plica tissues, and was to a lesser extent detectable in the fat pad of the patella, in the lateral borders of the patella and in the proliferated synovial tissues. Signs of degenerated axonal profiles were observed in these locations with a polyclonal antibody to the growth-associated protein GAP-43/B-50. At all the other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal.
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PMID:Innervation of the patella. An immunohistochemical study in mice. 751 3

The distributions of peptide-immunoreactive nerve fibres and cell bodies in lumbosacral paravertebral sympathetic ganglia of young cats were analysed with antibodies to calcitonin gene-related peptide, enkephalin, neurotensin, somatostatin, substance P, galanin, neuropeptide Y and vasoactive intestinal polypeptide. Fairly dense networks of nerve fibres showing enkephalin-, neurotensin-, somatostatin- or substance P-like immunoreactivity were observed in the ganglia. Double-staining experiments revealed that enkephalin- and somatostatin-immunoreactive nerve fibres preferentially surrounded calcitonin gene-related peptide- and/or vasoactive intestinal polypeptide-immunoreactive cell bodies. Neurotensin- and substance P-immunoreactive nerve fibres were mainly associated with neurons showing neuropeptide Y and/or galanin-like immunoreactivity. Occasional nerves containing calcitonin gene-related peptide-, galanin-, neuropeptide Y- or vasoactive intestinal polypeptide-like immunoreactivity were observed. These fibres did not seem to have any direct regional distribution within the ganglia. In kittens surviving for three months after early postnatal sciatic nerve resection, no calcitonin gene-related peptide-immunoreactive cell bodies could be detected in ganglia ipsilateral to the operation. In contrast, vasoactive intestinal polypeptide-like immunoreactivity, which partly co-exists with calcitonin gene-related peptide, was observed to the same extent as in control ganglia. Furthermore, almost all of the somatostatin-immunoreactive varicose nerve fibres had disappeared, whereas a fairly dense network of calcitonin gene-related peptide-immunoreactive nerve fibres could be observed. This change was paralleled by an increased content of nerve fibres that were immunoreactive to antibodies against the growth-associated protein GAP-43 (also known as B-50). The present findings suggest that experimental perturbations where postganglionic neurons are separated from their target areas by axotomy, not only induce differential changes in neurotransmitter expression in the principal ganglion cells, but also in preganglionic sympathetic neurons projecting to the ganglia. One possible explanation for the occurrence of an axotomy-induced network of calcitonin gene-related peptide-immunoreactive nerve fibres, is that extrinsic sensory nerve fibres grow into the ganglia after the sciatic nerve lesion. Thus, these findings seem to suggest one additional possibility with regard to the question of a possible interaction between sympathetic and sensory neurons after peripheral nerve injury.
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PMID:Peptide-immunoreactive neurons and nerve fibres in lumbosacral sympathetic ganglia: selective elimination of a pathway-specific expression of immunoreactivities following sciatic nerve resection in kittens. 769 Sep 13

The distribution of nerves and mast cells was studied in the lacrimal glands of 3-5-, 14- and 24-month-old rats, using light microscopic histochemical and immunohistochemical techniques. In 14-month and, to a greater extent, in 24-month-old rats there were signs of chronic inflammation and patchy destruction of acinar, ductal and vascular tissue. The glands of the three different age groups contained acetylcholinesterase (AChE), vasoactive intestinal polypeptide (VIP)-, neuropeptide Y (NPY)-, calcitonin gene-related peptide (CGRP)-, tyrosine hydroxylase-, substance P- and the phosphoprotein B-50-immunoreactive nerves. B-50-immunoreactive nerves were distributed around acini, blood vessels and ducts, in a similar manner to VIP and AChE. Substance P- and CGRP-immunoreactive nerves were sparsely distributed in interlobular connective tissue and around ducts and blood vessels. Tyrosine hydroxylase- and NPY-containing nerves were found around blood vessels. The 3-5- and 14-month-old rats had a similar pattern of innervation, however, by 24 months there was a reduction in the number and intensity of immunoreactive nerves. The loss of nerves was particularly associated with damage to the gland. Mast cells were also found in the lacrimal, mostly associated with neurovascular tissue. These could be histochemically labelled with alcian blue/safranin or toluidine blue and were immunohistochemically labelled with histamine and serotonin. Substance P-, CGRP-, VIP- and NPY-immunoreactive nerves were found apposed to mast cells. A large increase in mast cells was observed in 24-month compared to 3-5-month-old rats and these were found throughout the acinar tissue. These results show that a decrease in innervation and also chronic inflammation, with mast cell infiltration, occurs in aged rats. These findings may be contributing factors to reduced tear output in aging.
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PMID:Innervation and mast cells of the rat exorbital lacrimal gland: the effects of age. 818 88

The innervation of the rat and human anterior cruciate ligament, patellar tendon, and patellar tendon autograft after reconstruction of the anterior cruciate ligament was investigated by immunohistochemical and histological methods. A rat model of reconstruction with patellar tendon autograft was evaluated during active graft remodelling (2-16 weeks) and compared with normal ligament and tendon. The knees of 10 patients who had undergone reconstruction with patellar tendon autograft were examined 5-37 months postoperatively (remodeling fully completed) with arthroscopy and biopsy. As a control, biopsies from normal ligament and tendon were obtained from four patients. Nerve fibers were identified using antisera for protein gene product 9.5, a general neural marker. Neuronal regeneration was assessed by the expression of growth-associated protein 43/B-50. The sensory type of innervation was characterized by assessing the distribution of nerves containing the sensory neuropeptides calcitonin gene-related peptide and substance P. Immunoreactivity for all neural markers was found in both rat and human anterior cruciate ligament and patellar tendon. Two weeks after reconstruction, the rat autograft was acellular and no innervation could be identified. After 4 weeks, the grafts were viable, and immunoreactivity for protein gene product 9.5, growth associated protein 43/B-50, and calcitonin gene-related peptide was found until the 16th week postoperatively. Immunoreactivity for substance P was found in rat autografts at 4 weeks postoperatively only. All biopsies of human patellar tendon autograft showed signs of the remodelling process being fully completed, with revascularization and a sinusoidal collagen pattern with fibroblast repopulation. Neuropeptide immunoreactivity, however, was not found. The presence of immunoreactivity to sensory neuropeptides in the anterior cruciate ligament and patellar tendon may indicate a nociceptive and neuromodulatory function of these structures. The expression of sensory neuropeptides in the rat patellar tendon autograft suggests a possible involvement of sensory innervation during healing of the graft.
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PMID:Nerve regeneration during patellar tendon autograft remodelling after anterior cruciate ligament reconstruction: an experimental and clinical study. 864 95

We studied nerve ingrowth into a cancellous bone graft in a bone conduction chamber model in the rat. Before implantation of the chamber bilaterally in the proximal tibiae of 8 Sprague-Dawley rats, a defatted cancellous bone graft from separate donor rats was fitted snugly into each chamber. After 6 weeks, the animals were perfused with Zamboni's fixative and the chambers were harvested. Immunohistochemical detection of nerve fibers was performed in cryostat sections, using antisera to protein gene product 9.5 (PGP 9.5), neural growth-associated protein GAP-43/B-50, calcitonin gene-related peptide (CGRP), substance P and C- flanking peptide of neuropeptide Y (CPON). Nerve fibers were found in 10 out of 16 samples in the newly formed bone, and also in the fibrous tissue which had penetrated deeper into the graft. The nerve fibers were mainly of sensory origin, as they showed immunoreactivity for CGRP and GAP-43/B-50. We speculate that the nerve fibers may act as transmitters of nociceptive impulses from the graft, and as transport pathways for neuropeptides that are actively involved in angiogenesis and in the recruitment and activity of osteogenic cell populations from the graft recipient.
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PMID:Sensory nerve ingrowth during bone graft incorporation in the rat. 868 56

The effects of femoral and sciatic nerve resection on fracture healing and innervation of the fracture callus were studied using a stable fracture model. In 34 rats the right tibia was subjected to a standardized closed fracture and stabilized with a modular intramedullary nail. In half of the animals, resection of 1 cm of the femoral and sciatic nerves was performed (nerve resection group), whereas the other animals had sham operations (sham group). To avoid unequal load-bearing between the two groups, all fractured hindlimbs were immobilized in a plaster of Paris cast. The trial was terminated after 5 weeks of fracture healing. Callus size was scored radiographically, and bone mineralization was measured by 85-strontium incorporation. Seven rats from each group had immunohistochemical examination for neural regeneration and ingrowth. Antisera for protein gene product 9.5, neurofilaments, neural growth associated protein 43/B-50, calcitonin gene related peptide, and substance P were used. The mechanical properties of the healing fractures were recorded in a three-point cantilever bending test. After 5 weeks, the normally innervated, fractured tibias had regained approximately 50% strength compared with the unfractured side, in comparison with only 20% in the animals that had nerve resection. Although the fracture calluses were mechanically weaker, they were significantly larger in the nerve resection group, indicating defects in tissue composition or organization rendered by the nerve injury. The mineralization rate, as measured by 85-strontium incorporation, was the same in the two groups. However, the nerve resection did not provide complete denervation but changed the innervation pattern of the healing fracture, as the density of sensory nerve fibers immunostaining for substance P and neurofilaments was less in the group with femoral and sciatic nerve resection. The results suggest that intact innervation is essential for normal fracture healing because nerve injury induced a large, but mechanically insufficient, fracture callus.
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PMID:Fracture healing and callus innervation after peripheral nerve resection in rats. 964 67

The density of substance P (SP)-, calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) nerve endings was quantitatively evaluated in intact and inflamed gastrocnemius-soleus muscle of the rat. In persistently inflamed muscle (12 days after a single injection of Freund's adjuvant into the muscle), the density of SP-ir fibres was significantly increased. CGRP- and VIP-ir fibres displayed an insignificant increase in density. The density of fibres ir for nerve growth factor (NGF) and for growth-associated protein 43 (GAP-43/B-50), a marker for axonal sprouting, regeneration and synaptic reorganisation, increased significantly in persistently inflamed muscle. The data are consistent with the established contribution of NGF on the expression of SP and GAP-43 in afferent neurones under the influence of a persistent inflammation.
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PMID:Inflammation-induced increase in the density of neuropeptide-immunoreactive nerve endings in rat skeletal muscle. 969 86

We studied time-dependent ingrowth of sensory nerve fibers into a bone defect in a rat bone conduction chamber model. In 10 male Sprague Dawley rats, a titanium chamber was implanted bilaterally in the proximal tibiae, representing an experimental bone defect. To mimic a clinical situation, the chambers were filled with a fresh blood clot After 1, 2, 4, 6 and 8 weeks, 2 rats were fixed in vivo at each time before removal of specimens, and histological and immunohistochemical analyses. We used antisera against protein gene product 9.5, neural growth-associated protein 43/B-50, calcitonin gene-related peptide, and substance P, to locate regenerating sensory nerve fibers in the chamber. During bone defect healing, hematoxylin/eosin sections showed that new bone grew in through the ingrowth openings in the chamber, gradually filling it and replacing the blood clot. At 1 and 2 weeks after implantation, no nerve fibers could be detected. At 4, 6 and 8 weeks, however, small numbers of nerve fibers were seen in 8 of 11 specimens. The nerve fibers were located mainly in the dense fibrous tissue in close proximity to the new bone, and in some cases within the new forming bone. In this chamber model, the periosteum is not in contact with the bone ingrowth openings, and all ingrowing nerve fibers thus originated from the cortical bone, endosteum or bone marrow. We speculated that these late ingrowing sensory nerve fibers may actively participate in bone repair.
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PMID:Time-dependent sensory nerve ingrowth into a bone conduction chamber. 1074 98


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