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)

Employing a combination of retrograde tracing and immunocytochemistry, midbrain periaqueductal gray (PAG) neurons with substance P- or leucine-enkephalin-like immunoreactivity in the rat were found to send projection fibers to the nucleus accumbens bilaterally with an ipsilateral dominance. These neurons were most frequently seen in the ventrolateral and ventral parts of the medial PAG subdivisions at all rostrocaudal levels of PAG.
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PMID:Midbrain periaqueductal gray neurons with substance P- or enkephalin-like immunoreactivity send projection fibers to the nucleus accumbens in the rat. 170 15

By a double-labeling method combining the retrograde tracing of horseradish peroxidase and the immunocytochemical technique, serotonin-, substance P- or leucine-enkephalin-like immunoreactive neurons in the midbrain periaqueductal gray (PAG) and the nucleus raphe dorsalis (DR) of the rat were found to send projection fibers to the central amygdaloid nucleus bilaterally with an ipsilateral dominance. These PAG neurons were chiefly distributed in the ventrolateral PAG subdivision and the ventral parts of medial PAG subdivision at the middle and caudal levels of PAG.
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PMID:Serotonin-, substance P- or leucine-enkephalin-containing neurons in the midbrain periaqueductal gray and nucleus raphe dorsalis send projection fibers to the central amygdaloid nucleus in the rat. 170 70

Immunohistochemical studies for analysing the development of the profile of two peptides--substance P (SP) and Leu-enkephalin (Leu-ENK), and serotonin (SER)--have been conducted on the lateral geniculate nuclear (LGN) complex of albino rats at gestation day 18 and various postnatal age periods. SP immunoreactivity is found to increase from 1 day postnatal (DPN) up to 20 DPN and decrease thereafter, whereas the SER and Leu-ENK-immunoreactive fibres and terminals seen as occasional fibres at 1, 5, and 10 DPN are better visualized from 20 DPN and gradually increase up to 40 DPN. The possible role and significance of the changes seen in these putative neurotransmitters/neuromodulators with development are discussed.
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PMID:Development of substance P, Leu-enkephalin and serotonin profiles in the lateral geniculate nuclear complex of albino rat. 170 73

The IgA producing murine B lymphoma, CH12.LX.C4.4F10 (4F10) and the IgM producing murine lymphoma, CH12.LX.C4.5F5 (5F5) were found to express substantial numbers of substance P (SP) receptors having dissociation constants equal to 0.69 nM. Binding of SP by these B lymphoma cells was via the tachykinin-specific C-terminus sequence, Phe-X-Gly-Leu-Met-NH2, because SP, SP antagonist (D-Pro2-D-Phe7-D-Trp9-SP), eledoisin, and substance K could effectively inhibit radiolabeled SP binding, whereas the SP N-terminus fragment, SP (1-4), could not. The functionality of these receptors could be demonstrated by the ability of subnanomolar concentrations of SP to induce Ig secretion in a dose-dependent fashion. However, the presence of a second stimulus in these cultures was required to obtain maximal increases. IgA secretion by 4F10 cells was elevated only 25 to 37%, and IgM secretion by 5F5 cells was not significantly increased in cultures in which nanomolar concentrations of SP were present. Conversely, coculturing 5F5 cells with a suboptimal concentration of LPS (50 ng/ml) and 10(-10)M SP resulted in an approximate threefold increase in supernatant IgM when compared to control cultures stimulated with LPS alone. While not as dramatic, 10(-10) M SP also enhanced IgA secretion of LPS-stimulated 4F10 cells by approximately 45%. This enhancement of Ig secretion was SP-specific, as evidenced by the ability of 1000-fold excess of SP antagonist to block SP-induced, but not LPS-induced, Ig production. Clearly, SP could act synergistically with LPS to enhance Ig secretion; therefore, we questioned whether this augmentation was also reflected at the level of H chain mRNA expression. 10(-9)M SP induced modest increases (50 to 60%) in mu-chain mRNA expression by LPS-stimulated 5F5 cells when compared with cells stimulated with LPS alone. The 4F10 cells did not display this magnitude of difference for alpha-chain mRNA expression. Thus, although SP-induced increases of mu-chain mRNA by 5F5 cells may contribute to the increased Ig secretion observed by these LPS-activated lymphocytes, it is unlikely that increased mRNA expression can totally account for the threefold increases in secretion that were observed.
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PMID:Substance P acts directly upon cloned B lymphoma cells to enhance IgA and IgM production. 170 87

Immunocytochemical studies of the vestibular nuclei (VN) were done in the squirrel monkey and cat using polyclonal antisera. Brain stem sections were processed using the Avidin-Biotin peroxidase complex with diaminobenzidine as the chromagen. Choline acetyltransferase immunoreactivity (ChAT-IR) was most prevalent in the caudal medial (MVN), inferior (IVN) and peripheral superior (SVN) VN. Nearly all cells of groups x and z were ChAT-positive. None of the giant cells of the lateral vestibular nucleus (LVN) was ChAT-IR. Glutamate immunoreactivity (GLU-IR) was abundant in all VN and in cells of the vestibular ganglion (VG). Gamma-aminobutyric acid immunoreactivity (GABA-IR), was found in cells of rostral MVN, cell group y and in granules about giant cells in dorsal LVN. Substance P immunoreactive (SP-IR) was present in a small cells in MVN, IVN and the VG and in granules surrounding all large cells in LVN in both monkey and cat; SP-IR granules were most intense in ventral LVN in the monkey. Some cells in the dorsal parts of the fastigial nucleus (FN) were outlined by SP-IR granules in both species. Leucine-enkephalin immunoreactivity (ENK-IR) was identified only in granules surrounding cells of group x in the monkey. GLU was the only immunoreactive substance found in the giant cells of LVN. The disposition of ChAT-IR in the VN suggested participation in commissural systems, as well as projections to spinal cord and/or cerebellum. Small GABA-IR neurons in MVN probably represented both commissural and projection neurons; GABA-IR granules about cells in dorsal LVN and some cells in MVN and SVN appeared to represent Purkinje cell (PC) terminals. SP-IR granules surrounding cells in ventral LVN appeared to represent terminals of small SP-positive VG cells. The source of SP-IR granules around cells in dorsal LVN and some cells in FN and SVN remains unknown, but these fibers may originate from portions of the reticular formation known to contain large numbers of SP-positive neurons.
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PMID:Immunocytochemical features of the vestibular nuclei in the monkey and cat. 170 74

Retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was studied in 7 squirrel monkeys with discrete injections of the subthalamic nucleus (STN). Injections labeled: (1) the lateral two-thirds of the nucleus (63% and 47%), (2) ventrolateral parts caudally (20%), (3) dorsomedial parts caudally (18%), (4) rostromedial parts (21%), (5) the medial third (38%) and (6) the lateral pole of the nucleus (9%). Afferents to the lateral two-thirds of the STN originated from two parallel cellular arrays in dorsal parts of the middle third of the lateral pallidal segment (LPS) and a single array in the rostral third of the LPS. Medial regions of the STN received input from cells in the rostral LPS. Small numbers of cells were retrogradely labeled in the centromedian-parafascicular (CM-PF) and the pedunculopontine (PPN) nuclei. No cells were labeled in the frontal cortex, the striatum, the substantia innominata (SI), the substantia nigra (SN) or the dorsal nucleus of the raphe. Virtually all pallidal neurons, including identified pallidosubthalamic neurons, were immunoreactive (IR) for gamma-aminobutyric acid (GABA). Pallidosubthalamic neurons were most numerous in regions of the LPS with the lowest density of leucine enkephalin-IR fibers. Substance P-IR fibers, found mainly in the medial pallidal segment, bore no relationship to pallidal afferents to the STN. Choline acetyltransferase-IR cells in the SI and the PPN were not retrogradely labeled with WGA-HRP granules. Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS, suggesting a reciprocal relationship. The caudal third of the LPS and ventral region of the middle third of this nucleus, appeared to project few fibers to, or to receive few fibers from, the STN. A small number of STN efferents entered the medial border of the putamen, but no terminal fields were identified. STN projections to the pars reticulata of the SN appeared to represent about 10% of the projection to the LPS. No STN efferents were identified in the frontal cortex, the SI or the PPN. The hypothesis that STN afferents from the frontal cortex and CM-PF may represent collaterals of projections to other loci is discussed.
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PMID:Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents. 170 79

The outer cortex of the human thymus contains a one- to two-cell-thick layer that is immunoreactive with antisera against beta-endorphin, (Leu)- and (Met)-enkephalin, bombesin, and substance P. The epithelial nature of these immunostained cells is revealed by immunoelectron microscopic studies showing the presence of desmosomal junctions. The presence of peptide-containing cells in the outer cortex, where the most immature and recently immigrated thymocytes are found, emphasizes the role of neuropeptides in regulating the microenvironment for T cell development.
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PMID:Neuropeptide-immunoreactive cells in human thymus. 170 21

The catabolism of substance P and bradykinin, two peptides involved in inflammation, by human neutrophils was investigated. Substance P was cleaved by unstimulated neutrophils, but the rate of hydrolysis increased greatly (about 4-fold) when the cells were lysed by freezing and thawing or stimulated to release with fMet-Leu-Phe and cytochalasin B. The enzyme responsible for cleaving substance P was cathepsin G, hydrolyzing the Phe7-Phe8 bond. Neutral endopeptidase 24.11 (enkephalinase) became the main inactivating enzyme only when neutrophil cytoplasts (containing plasma membrane but no subcellular particles) or washed plasma membrane enriched high speed sediments were tested. Subcellular fractionation showed the highest substance P degrading activity to be in the granules. Purified cathepsin G readily cleaved substance P with a Km of 1.13 MK, a kcat of 6.35 sec-1 and a kcat/Km of 5639 M-1 sec-1, similar to kinetic constants previously reported for the best peptide substrates of cathepsin G. Despite the high Km, purified cathepsin G did hydrolyze SP at a much lower substrate concentration (down to 1 nM) as determined by radioimmunoassay. Bradykinin was also hydrolyzed by intact neutrophils but, in contrast, was not inactivated by cathepsin G, but by neutral endopeptidase at the Pro7-Phe8 bond. The inactivation of bradykinin by intact neutrophils was decreased by phorbol 12-myristate 13-acetate, probably due to down-regulation by endocytosis of the neutral endopeptidase on the plasma membrane. Thus, both bradykinin and substance P are inactivated by human neutrophils, although by different enzymes. In spite of the less favorable kinetics in vitro than with neutral endopeptidase, cathepsin G is the main inactivator of substance P in neutrophils. This may be due to the estimated 300 to 3600-fold higher concentration of cathepsin G in neutrophils than that of the neutral endopeptidase.
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PMID:Metabolism of substance P and bradykinin by human neutrophils. 170 55

A new hexapeptide analog of Substance P, containing a C-terminal thioamide group in the molecule [( Glp6, Mett11]SP6-11) was synthesized: Glp-Phe-Phe-Gly-Leu-Mett-NH2. Conversion to thioamide was accomplished from tert-butoxycarbonyl-L-methionine amide (Boc-Met-NH2) using Lawesson's Reagent. Its contracting activity on isolated guinea-pig ileum was considerably lower than that of [Glp6]SP6-11.
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PMID:Synthesis and some biological properties of the hexapeptide analog of substance P with a C-terminal thioamide group. 171 85

The sea urchin hatching enzyme (HEz) is a protease capable of dissolving the fertilization envelope that surrounds the embryo as a protective coat during early development. We have now purified a 37-kDa active enzyme from the supernatant fluid of hatched blastula medium of the species Hemicentrotus pulcherrimus. The purified enzyme was completely inhibited by alpha 2-macroglobulin and the chelating agents EDTA, EGTA, and 1,10-phenanthroline and was slightly inhibited by chymostatin and pepstatin, but was not inhibited by various other serine and thiol protease inhibitors. These results suggest that HEz is a metalloproteinase. Quantitative analyses of the products of HEz's action on various peptides revealed that the enzyme preferentially cleaved the peptide bonds on the amino side of bulky hydrophobic residues, -Leu, -Ile, and -Phe as well as -Tyr, in a similar but more limited fashion than thermolysin. Furthermore, although substance P was a good substrate of HEz, snake venom alpha-protease, and thermolysin, the analogue [Sar9]substance P was a poor substrate for HEz. This analogue was a good substrate for thermolysin and alpha-protease, but the scissile bonds were altered from those of substance P. The failure of HEz and alpha-protease to cleave the P1-P1 bond that meets the primary specificity is ascribed to the presence of an imino acid residue (proline or sarcosine) or the absence of any amino acid at the P2h or P3' position, in contrast to the simple P2' restriction of thermolysin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The specificity of sea urchin hatching enzyme (envelysin) places it in the mammalian matrix metalloproteinase family. 171 95


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