Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The unlabeled substance P (SP) antibody-peroxidase-antiperoxidase reaction was used on tissue prior to embedding in epoxy reins for ultrastructural identification of the SP cell and its immunoreactive granules. The SP cell is 10-20 mum in diameter and has sparse cytoplasm with numerous intensely reactive SP granules 100-300 nm across, large clear vacuoles, elaborate smooth endoplasmic reticulum, fragmentary rough endoplasmic reticulum, dispersed ribosomes, few mitochondria, and a modest Glogi apparatus. The large SP-reactive granules are discharged into the extracellular space, either with cell membrane intact or as unbound dense material. The membrane-bound dense granucles are transported intact through endothelial cells into the blood or are picked up by Schwann cells and fibroblasts. Other SP-reactive granules lose their limiting membranes, fragment, and then disperse into fine immunoreactive grains that bind to the extracellular matrix and to collagen. Dispersed SP-reactive granules are transported within myriad pinocytotic vesicles across endothelial cells with numerous luminal plications and are discharged into the blood. Pinocytosis of dispersed SP-reactive material, that can be detected intracellularly, also occurs in Schwann cells and fibroblasts. The SP axons to the substantia gleatinosa are unmyelinated or finely myelinated. Their synaptic varicosities display a generalized axoplasmic immunoreactivity, which also occurs in and around small vesicles. The larger SP synaptic vesicles are intensely reactive.
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PMID:Ultrastructural identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord by immunocytochemistry. 33 57

The activity and distribution of substance P-catabolizing enzyme(s) were studied in the rat kidney. Kidney homogenates inactive substance P 5-20 times as fast as do homogenates of intestine, liver, lung, heart or brain. The catabolizing activity was highest in the cortex and decreased progressively down the papilla. Cortex of rat kidney was homogenized and fractions enriched in microsomal membrane, final supernatant, plasma membrane, endoplasmic reticulum, brush border and intact glomeruli were prepared. The identity and homogeneity of the preparations were determined by assaying marker enzymes and by morphological examination. Substance P was catabolized most rapidly by the microsomal and plasma-membrane-enriched fractions, and least rapidly by endoplasmic reticulum or final supernatant fractions. Purified brush border of proximal tubules inactivated substance P more than 10 times as fast as isolated glomeruli. Our experiments show that substance P is catabolized at a rate that is similar to the rates of inactivation of bradykinin and angiotensin II. Further, the distribution of substance P-catabolizing activity in various kidney fractions is similar to the distribution of kininase and angiotensinase activities previously reported.
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PMID:Renal inactivation of substance P in the rat. 64 14

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.
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PMID:Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. 127 91

90 primary breast carcinomas and 18 metastases were immunostained for c-erbB-2 protein and neuron specific enolase. 30 tumours were c-erbB-2 negative and NSE positive, 23 tumours were NSE negative and c-erbB-2 positive. 1 tumour expressed focal immunoreactivity for both markers. 54 of the 108 tumours (50%) did not express either marker. Hormone immunoreactivity was present in single cells and in small groups of cells in 18 of the 31 NSE positive tumours. Bombesin, neurotensin and prealbumin were present in 4 cases each, followed by beta-endorphin and VIP in 3 cases each, leu-enkephalin in 2 cases and gastrin, serotonin, substance P, glucagon and somatostatin in 1 case each. None of 10 NSE negative breast carcinomas were comprised of cells expressing immunoreactivity for hormones. By immunoelectron microscopic examination the c-erbB-2 protein was shown to be present on the cell membrane, on smooth areas, microvilli and in coated pits. Immunoreactivity was also expressed in vesicles in cytoplasm and along rough endoplasmic reticulum. The study shows that c-erbB-2 protein expression and neuroendocrine activity are present in different tumour cell populations. This supports the hypothesis that the presence of c-erbB-2 protein, indicating an elevated cellular tyrosine kinase activity with stimulation of growth, intracellular Ca++, and phosphatidylinositol derivates, means that the same cell does not need regulation of the same factors by stimulation of peptide hormone receptors. Thus the production of autocrine and paracrine factors is switched off.
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PMID:C-erbB-2 protein and neuroendocrine expression in breast carcinomas. 167 29

Substance P (SP) is a non-opioid peptide that generates a potent analgesia when injected into the periaqueductal gray matter (PAG). The aim of this study was to investigate the fine neuronal structures and synaptic circuits involved in SP action in rats by means of electron microscopy, using immunocytochemical (ICC) pre-embedding methods. A conventional ultrastructural study, carried out to interpret the ICC data correctly, shows small sized nerve cell bodies with a high nucleus-cytoplasmic ratio; absence of an extensive granular endoplasmic reticulum; and few axo-somatic contacts having symmetrical and asymmetrical junctions in equal proportions. The large neuropil is characterized by numerous thin unmyelinated axons and axo-dendritic synapses mainly showing pleomorphic vesicles and asymmetrical junctions. The ICC analysis showed moderately labeled nerve cell bodies with the same structural, synaptic, and dimensional features as the negative cells. In the neuropil SP immunoreactivity is shown by dendrites, synapses, and thin elements which are unidentifiable structurally. No SP terminals synapsing on SP nerve cell bodies were found and only occasional SP light labeled terminals synapsing on negative perikarya were seen. The SP boutons generally have pleomorphic vesicles and asymmetrical junctions. On the basis of these data a possible excitatory activity of PAG SP synapses could be hypothesized. This activity would take place on postsynaptic neurons generally at a dendritic level. Our ultrastructural findings give support to an excitatory role carried out by SP neurons of the PAG, as suggested by the role of PAG circuitry on spinal nociception.
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PMID:Ultrastructure of substance P immunoreactive elements in the periaqueductal gray matter of the rat. 170 83

An increase in inositol 1, 4, 5-trisphosphate (IP3) formation in rat mast cells precedes an elevation in intracellular Ca2+ levels, which triggers the process(es) leading to histamine release. By means of a transmission electron microscope, it was revealed that when permeabilized mast cells were exposed to potassium antimonate, antimonate precipitates in the endoplasmic reticulum (ER) in the form of calcium antimonate, indicating that the ER is the intracellular Ca store in rat mast cells. IP3 at concentrations higher than 0.5 microM preferentially releases Ca2+ from the isolated ER of mast cells. GTP was also effective in releasing Ca2+ from the ER. IP3-induced Ca2+ release was inhibited by pretreatments with cAMP and antiallergic drugs. An increase in the intracellular Ca2+ concentration may lead to an activation of calmodulin, C kinase and cytoskeletal elements in sequence. Furthermore, microtubules may play an important role in the process(es) leading to Ca2+ release from the intracellular Ca store and subsequent histamine release, without affecting IP3 formation. In contrast, microfilaments seem to participate not only in the extrusion but also in the reincorporation of the mast cell granules, having no influence on intracellular Ca2+ release. Substance P (SP) is one of the most effective neuropeptides for releasing histamine from mast cells. Structure-activity relationship studies indicate that basicity at the N-terminal and hydrophobicity at the C-terminal are requisite for its histamine releasing activity. SP effectively released Ca2+ from the intracellular Ca store. The site of action of SP on the mast cell surface seems to be the same as that of compound 48/80. Eosinophil major basic protein (MBP) and histone are also effective for releasing histamine. The cDNA sequences of two subclasses of guinea pig MBP have been determined. These proteins may be released at the site of inflammation from the cells activated by the chemical mediators released from mast cells, and consequently, mast cell activation was reinforced. Such cell-to-cell interaction may be the reason for the augmentation of inflammation.
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PMID:[Recent advances in the research on histamine release]. 172 Jul 58

The neuronal population of dorsal root ganglia in mouse consists of various classes of ganglion cells which may be divided in turn into subclasses by using several criteria. In class A cells, membrane-bound organelles are distributed ubiquitously throughout the large perikarya. Subclass A alpha (12%), which is characterized by large clumps of Nissl substance separated by narrow strands of neuroplasm, lacks detectable carbonic anhydrase activity. Subclass A beta (16%) displays small clusters of Nissl substance isolated by broad channels of neuroplasm and a moderate activity of carbonic anhydrase. Subclass A gamma (8%) shows the most intense carbonic anhydrase activity and a lack of uptake for [3H]L-glutamine. In class B cells (63%), the small perikarya display a zonal distribution of the organelles. Subclass B alpha contains parallel cisternae of rough endoplasmic reticulum and acid phosphatase isoenzymes present in long and curved Golgi saccules. Subclass B beta displays straight Golgi saccules rich in acid phosphatase isoenzymes and a high affinity uptake for glutamine. Subclass B gamma is characterized by the absence of acid phosphatase isoenzymes and by the presence of substance P-immunoreactivity. Class C cells (1%) have the smallest size and the highest affinity uptake for glutamine. Thus subtypes of primary sensory ganglion cells may be identified by the concomitant use of multiple criteria.
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PMID:Neuronal subpopulations in the dorsal root ganglion of the mouse as characterized by combination of ultrastructural and cytochemical features. 241 65

Two immunocytochemical methods, immunoperoxidase and immunogold (IG), were used in an attempt to study the dynamic process of prolactin release from stimulated rat pituitary mammotrophs. The immunogold method was also used to localize other pituitary hormones including growth hormone, follicle-stimulating hormone, luteinizing hormone, and the neuropeptides substance P, neuropeptide tyrosine, leu-enkephalin, and atrial natriuretic factor in peripheral nerves. Light-microscopic immunoperoxidase staining of prolactin revealed a unique distribution of immunoreactive mammotrophs. Two groups of cells were seen, one centrally located and one forming a narrow peripheral rim on the gland. The two groups were separated by a zone of nonimmunoreactive cells. In addition, the distribution of immunoperoxidase-stained material was not uniform in all mammotrophs. In some, prolactin immunoreactive material was clumped near the nucleus (in the Golgi cisternae); in others it was more diffused within the cytoplasm (but immediately surrounding the cisternae of rough endoplasmic reticulum). After stimulation of mammotrophs, via suckling, prolactin-immunoreactive material was visualized in extracellular spaces. With immunogold methods, prolactin labelling was seen mainly in secretory granules; but some labelling of Golgi cisternae and rough endoplasmic reticulum also occurred. Immunogold labelling revealed that material immunoreactive for leu-enkephalin and atrial natriuretic factor was present in nerve terminals in the rat paracervical ganglion. Material immunoreactive for substance P and neuropeptide tyrosine was present in nerve terminals in the guinea pig heart. Thus, in some situations the immunoperoxidase technique was useful and helped to visualize "grossly" the presence of specific antigens, but it was inadequate for fine ultrastructural localization of these antigens. The immunogold technique was excellent for precise localization of antigens and especially for the detection of colocalization of different antigens. This method can be used in very different structures, such as the adenohypophysis and peripheral nervous tissue, without any modification except for the nature of the antibodies.
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PMID:Use of immunoperoxidase and immunogold methods in studying prolactin secretion and application of immunogold labelling for pituitary hormones and neuropeptides. 242 15

Rat's temporal cortex was cultured in vitro in a feeding medium enriched with substance P. Normal controls were used for correlation. The ultrastructural study of the explant exposed to substance P revealed a marked increase of the polymorphism of the synaptic vesicles in the presynaptic terminals. Large numbers of the synaptic vesicles were large, of a mean diameter of 142.5 A, dark-looking like the catecholaminergic vesicles. Coated vesicles were seen in the presynaptic terminals as well as in the postsynaptic ones. Large elongated vesicles and S-like vesicles were seen in the axonic terminals mainly in axosomatic synapses and in axodendritic synapses with large dendritic profiles. In most of the synapses, a remarkable thickness of the postsynaptic membrane was noticed. In a large number of postsynaptic terminals, the cisternae of the smooth endoplasmic reticulum were dilated and intermixed with dilated vesicles and fragmented microtubules. Some of the presynaptic terminals demonstrated marked thickness of the presynaptic membrane. Glycogen granules were frequently seen in the postsynaptic terminals. In conclusion, substance P administered in vitro, increases the polymorphism of the synaptic vesicles in the presynaptic terminals of neurons derived from the temporal isocortex.
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PMID:Substance P increases the polymorphism of the synaptic vesicles in the temporal isocortex cultured in vitro. 245 65

Cerebrospinal fluid (CSF)-contacting neurons are located periventricularly or inside the brain ventricles; they contact the CSF via their dendrites, perikarya or axons. Most of these neurons form ciliated dendrite terminals in the internal CSF as do retinal and pineal photoreceptors in the optic ventricle and pineal recess. The peculiar localization, polarization and synaptic connections of the CSF-contacting neuronal elements suggest receptor and integrative functions. The present review pays special attention to vitamin A (retinoids) immunoreactivity in CSF-contacting neurons as compared with that present in retinal and pineal photoreceptor cells, common neurons, glial and adenohypophysial cells. The immunoreactivity of the dark-adapted photoreceptor outer segments was strong, but decreased after illumination, suggesting the functioning of vitamin A as the chromophore of the retinal and pineal photopigments. Retinoid immunoreaction was also found in the endoplasmic reticulum, nuclei, nucleoli and mitochondria of the cell types studied. This cytological localization suggests that vitamin A compounds may be involved in the function of these organelles. The CSF-contacting neurons contain varying amounts of bioactive materials. The intracellular distribution of immunoreactive serotonin (5-HT), substance P (SP) and gamma-aminobutyric acid (GABA) is compared with that of immunoreactive vitamin A. Immunogold labeling for SP was demonstrated in dense-core vesicles of preoptic neurons; 5-HT marking was found on the dense-core vesicles of subependymal CSF-contacting neurons of the paraventricular organ, while GABA immunoreaction was localized in the cytoplasm of distal infundibular CSF-contacting neurons. The CSF-contacting neurons are considered to synthesize and release their bioactive substances at transmitter synapses, and/or at neurohormonal terminals into the external CSF in accord with information received by their dendrites from the internal CSF and by afferent fiber connections from various brain areas.
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PMID:The cerebrospinal fluid-contacting neuron: a peculiar cell type of the central nervous system. Immunocytochemical aspects. 247 2


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