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 purpose of this study was to assess the relationship of neuropeptide nerves and inflammatory leukocytes in PVG rats with adjuvant-induced arthritis. Substance P- and calcitonin gene-related peptide (CGRP)-immunoreactive nerves and inflammatory leukocytes were studied, using peroxidase (ABC) and/or alkaline phosphatase (APAAP) staining. Inflamed synovial tissue proper was infiltrated with neutrophils, ED1 macrophages and focal accumulations of CD2 T lymphocytes. In such tissue, the relationship between peptide-immunoreactive nerves and inflammatory cells was such that substance P and CGRP nerves were absent in heavily infiltrated villous synovial tissue, whereas healthy synovial tissue and non-inflammatory areas in adjuvant arthritic rats were innervated by substance P and CGRP nerves close to normal synovial tissue resident cells. In order to elucidate an eventual mechanism for lost immunoreactivity, healthy synovial tissue was exposed to chymotrypsin or oxygen derived free radicals (ODFR) in vitro. The former treatment caused total loss of immunoreactivity. These findings suggest that neuropeptides and neuropeptide containing nerves may be destroyed by locally produced proteolytic enzymes and various reactive oxygen species in the vicinity of inflammatory cells.
 ...
PMID:Relationship between neuropeptide immunoreactive nerves and inflammatory cells in adjuvant arthritic rats. 137 4

Fluorescent dextran amines have recently been reported to be useful for anterograde pathway tracing. However, fluorescent markers are not always ideal for detailed mapping studies. We therefore evaluated the efficacy of a biotinylated dextran amine (BDA) for anterograde labeling in several different preparations. BDA was visualized with an avidin-biotinylated HRP (ABC) procedure followed by a standard or metal-enhanced diaminobenzidine (DAB) reaction. After iontophoretic injections of BDA into neocortex-like telencephalic regions in pigeons or into visual or somatosensory cortex in rats, there was excellent and abundant labeling of axons and terminals in forebrain, midbrain and hindbrain target areas with 1-week survival times. Large pressure injections of BDA into the avian telencephalon were also found to result in extensive anterograde labeling. We then carried out a series of studies using 2-color DAB double-labeling to determine effective approaches for combining BDA labeling with other labeling methods. Using an isolated embryonic chick spinal cord-hindlimb preparation, we combined BDA labeling with another anterograde labeling method to differentially label two sets of projections. In these studies, sensory neuron and motoneuron projections into the limb from the same segmental level, or motoneuron projections into the limb from two separate segments were differentially labeled by using HRP (visualized first with a blue/black metal-DAB reaction) and BDA (visualized second with a brown DAB reaction). In other double-labeling studies, we combined BDA labeling of axons and terminals with immunohistochemical labeling of neurons. In these experiments, telencephalic neurons in pigeons or rats were labeled immunohistochemically for parvalbumin or substance P (using a brown DAB reaction) and BDA-labeled axons were labeled blue/black (using a metal-intensified DAB reaction). Double-labeling was successful regardless of whether the entire immunohistochemical labeling procedure preceded or followed the BDA labeling procedure. Together, these studies show that BDA is effective for anterograde pathway tracing and can be used in double-label studies with other labeling methods.
 ...
PMID:Biotinylated dextran amine as an anterograde tracer for single- and double-labeling studies. 138 Oct 34

Six pairs of rats were used in the experiment. The sciatic nerve was stimulated in one of every pair with the electric needle. Then the substance P (SP-like immunoreactive nerve fibers in the nucleus of the solitary tract (NST) were showed with immunohistochemical technique (ABC METHOD). The other of every pair was as the control. All experimental procedures were the same as the electroacupuncture group except that the sciatic nerve wasn't stimulated. The contents of SP of NST (at the area postrema segment) of both the electroacupuncture and the control were measured with the micro-spectroscopic image analyser. The results obtained were as follows: 1. The distribution positions of SP-like immunoreactive nerve fibers in the electroacupuncture group were the same as in the control group. That is, SP-like immunoreactive nerve fibers distributed from the caudal part to the rostral part in NST. 2. The contents and the area of SP-like immunoreactive nerve fibers of the electroacupuncture were more than the control. There was a significant difference between the two groups. The results mentioned above suggested that the role of NST is involved in the acupuncture analgesia.
 ...
PMID:[Effect of electroacupuncture on the contents of substance P in the nucleus of the solitary tract in rats]. 171 1

The regional distribution of substance P in postmortem brain and spinal cord of 5 cases of schizophrenia were investigated using the immunohistochemical PAP and ABC technique. Substance P immunoreactive fibers were primarily found in Substantia nigra, nucleus tractus spinalis n. trigemini, nucleus tractus solitarii, nucleus spinalis n. vestibuli, nucleus ambiguous, Central gray matter of the midbrain, globus pallidus and cornua posteriora spinales. The 5 cases showed no differences to the controls. These results agree with the finding reported abroad that the brain tissues were measured by radioimmunoassays. It was also discussed on study method of substance P in Central nervous system.
 ...
PMID:[Observations on substance P in the brain and spinal cord in schizophrenia]. 248 3

This experiment aimed to explore the effects of substance P (SP) on secretory otitis media (SOM). Both immunohistochemistry ABC-GDN and image pattern analysis technique were adopted to investigate the relation between SP content of SOM middle ear mucosa and middle ear effusion, and observe the effect of SP receptor antagonist spantide and histamine H2 receptor blocker cimetidin on middle ear effusion. The findings showed: middle ear mucosa SP content tended to increase, and had positive correlation with middle ear effusion, intra-abdominally injecting 1 mg/ml Spantide and 1 mg/ml Cinetidin per day could have middle ear effusion decreased obviously, but the quantities of reduction were more significant. The results suggest that SP plays a role in SOM, might accelerate vasodilation and increase the permeability of cupillary in middle ear mucosa mediated by histamine.
 ...
PMID:[The effect of substance P upon middle ear effusion of secretory otitis media and the mode of action]. 981 2

The occurrence of substance P (SP) immunoreactivity was investigated in the adrenal gland of the lizard Podarcis sicula by ABC immunocytochemical technique: SP-immunoreactivity was present in both adrenaline and noradrenaline cells, in ganglion cells and nerve fibers in the connective capsule surrounding the gland. The involvement of substance P in the modulation of pituitary-interrenal axis was studied in vivo by intraperitoneal injections of SP. The effects were estimated by means of the morphological and morphometrical features of the tissues, as well as the plasma levels of adrenocorticotropic hormone (ACTH), corticosterone and catecholamines, adrenaline and noradrenaline. Substance P (0.07 mg/100 g body wt) decreased ACTH plasma levels and raised corticosterone release from steroidogenic tissue, that showed clear signs of stimulation. In the chromaffin tissue, the decrease in the number of noradrenaline cells, and the increase in the number of adrenaline cells, lowered numeric noradrenaline/adrenaline cell ratio. Moreover, an increase in adrenaline plasma level and a decrease in noradrenaline plasma level were found. The results suggest that (1) also in Reptiles as in other Vertebrates, SP may affect pituitary-adrenal axis activity, and (2) the chromaffin cells may be involved in the paracrine control of steroidogenic activity.
 ...
PMID:Immunocytochemical localization of substance P in the adrenal gland of Podarcis sicula (Reptilia, Lacertidae): evidence for its involvement in the modulation of adrenal activity. 1463 29

Mechanical stimuli are known to have major influences on chondrocyte function. The molecular events that regulate chondrocyte responses to mechanical stimulation have been the subject of much study. Using an in vitro experimental system we have identified mechanotransduction pathways that control molecular and biochemical responses of human articular chondrocytes to cyclical mechanical stimulation, and how these responses differ in cells isolated from diseased cartilage. We have previously shown that mechanical stimulation of normal articular chondrocytes leads to a cell membrane hyperpolarisation. Within 1 hour following mechanical stimulation there is an increase in aggrecan mRNA levels. These responses are mediated via alpha5beta1 integrins, the neuropeptides substance P and NMDA, and the cytokine interleukin-4. In OA chondrocytes mechanical stimulation leads to cell membrane depolarisation, but no change in aggrecan mRNA at 1 hour. The depolarisation response is mediated via alpha5beta1 integrins, substance P and interleukin-4, but the cells show an altered response to NMDA. Having identified that the NMDA receptor is present in human articular cartilage and may play an important role in a chondroprotective mechanotransduction pathway, we were interested in whether other components associated with NMDA signalling may be involved in the chondrocyte mechanotransduction pathways. One such component is calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII mediates many cellular responses to elevated Ca2+ in a wide variety of cells and tissues. It is involved in the regulation of ion channels, cytoskeletal dynamics, gene transcription, neurotransmitter synthesis, insulin secretion, and cell division. CaMKII also shows a broad substrate specificity and is abundant in brain tissue, indicating that this kinase may play a number of roles in the functioning of the central nervous system. This kinase has been studied extensively in brain, but there is only a limited understanding of CaMKII in other tissues. CAMKII has four subunit isoforms (alpha,beta,gamma,delta). The alpha- and beta-isoforms have narrow distributions restricted mainly to neuronal tissues, but the gamma- and delta-isoforms are ubiquitously expressed within neuronal and non-neuronal tissues. The aim of this study was to investigate the expression of CaMKII in normal and OA cartilage and chondrocytes, and whether this enzyme is involved in the response of chondrocytes to cyclical mechanical stimuli. Reverse transcriptase-polymerase chain reaction (RT-PCR), using primers specific for the different CaMKII isoforms, was carried out to assess which isoforms are expressed in human articular chondrocytes. To assess whether CaMKII is expressed in human articular chondrocytes at the protein level, cultured chondrocytes were extracted and analysed by Western blotting using a pan-CaMKII antibody. Immunohistochemistry was carried out to investigate whether CaMKII is expressed by human articular chondrocytes in vivo. Frozen sections of normal, OA and ankle cartilage were incubated for one hour with CaMKII antibody and visualised using ABC and DAB. To assess the role of CaMKII in the mechanotransduction responses of normal and OA chondrocytes, human normal and OA articular chondrocytes were mechanically stimulated at 0.33 Hz, or by addition of recombinant IL-4 for 20 minutes. Cell responses to these stimuli, in the absence or presence of an inhibitor of CaMKII were assessed by measuring changes in cell membrane potential or changes in relative levels of aggrecan mRNA compared with the housekeeping gene GAPDH. Normal, OA, and ankle chondrocytes expressed the gamma and delta isoforms of CaMKII mRNA, but not the alpha and beta isoforms as demonstrated by RT-PCR. Western blotting showed a band at approximately 60 kDa consistent with the expression of CaMKII. Immunohistochemistry revealed the positive staining in the middle and deep zones, but not the superficial zone, of normal, OA, and ankle cartilage. The presence of a CaMKII inhibitor inhibits the membrane hyperpolarisation response and upregulation of aggrecan mRNA in normal chondrocytes following mechanical stimulation, but has no effect on the hyperpolarisation response to recombinant IL4. The depolarisation response of OA chondrocytes to mechanical stimulation is unaffected by the presence of the CaMKII inhibitor. The CaMKII isoforms gamma and delta are expressed in both normal and OA chondrocytes, both in vitro and in vivo, but are only involved in the response of normal chondrocytes to mechanical stimulation. This response is upstream of the effect of IL4. These findings are consistent with previous findings for the NMDA receptor, and suggest that dysregulation of NMDA-CaMKII signalling may be important in onset and progression of osteoarthritis.
 ...
PMID:Calcium/calmodulin-dependent protein kinase II in human articular chondrocytes. 1691 96

The intrahepatic distribution of nerve fibres is highly species dependent, therefore we searched for a species where the innervation pattern is similar to that of the human liver. Livers of rats, cats, guinea pigs and humans were used. The different nerve elements were identified by ABC immunohistochemistry and analysed semiquantitatively. Large numbers of neuropeptide Y (NPY) and dopamine-beta-hydroxylase immunoreactive (IR) nerve fibres were observed in the human and guinea pig liver, and they were in close contact with portal triads, central veins and ran parallel with liver sinuses. A few substance P, somatostatin and vasoactive intestinal polypeptide IR nerve fibres were also detected intralobularly, while galanin nerve fibres were only observed around portal triads. In the rat liver only a few NPY-positive nerve fibres were found, exclusively in portal tracts. Some nerve cell bodies (IR for NPY and somatostatin) were also found in the liver of guinea pigs, young cats and humans, therefore some of the nerve terminals might originate from these intrinsic ganglia. It can be concluded that the innervation pattern of the guinea pig liver shows the highest similarity to that of the human liver.
 ...
PMID:Distribution and possible origin of neuropeptide-containing nerve elements in the mammalian liver. 2046 Feb 17