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)

Endopeptidase 24.15 (EP 24.15; EC 3.4.24.15), a zinc-metalloendopeptidase purified from rat brain and testes and also present in many other tissues, including the lung, degrades substance P, neurotensin, bradykinin, luteinizing hormone-releasing hormone, and some other bioactive peptides. The enzyme, present both as soluble cytoplasmic and membrane-bound forms, also rapidly converts dynorphin, alpha- and beta-neoendorphin, and some other opioid peptides into their respective enkephalins. In this study, a rabbit antibody to EP 24.15 purified from rat testes was used to study distribution of the enzyme in rat trachea, lung tissue, and alveolar macrophages (AMs) by immunohistochemical techniques. We found intense immunoreactivity to EP 24.15 within the cytoplasm of ciliated epithelial cells of tracheobronchial mucosa extending from trachea to terminal bronchioles. In addition, large myelinated paratracheal and peribronchial nerve fibers showed immunoreactivity. Blood vessels and alveolar lining cells were negative. AMs also showed intense diffuse cytoplasmic immunoreactivity. The findings of EP 24.15 immunoreactivity in airway epithelium, AMs, and paratracheal and peribroncheal nerve fibers suggest that the enzyme may modulate the activities of bioactive peptides within the lung.
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PMID:Immunohistochemical localization of endopeptidase 24.15 in rat trachea, lung tissue, and alveolar macrophages. 225 85

The catabolism of two gastric neuropeptides, the C-terminal decapeptide of gastrin releasing peptide-27 (GRP10) and substance P (SP), by membrane-bound peptidases of the porcine gastric corpus and by porcine endopeptidase-24.11 ("enkephalinase") has been investigated. GRP10 was catabolized by gastric muscle peptidases (specific activity 1.8 nmol min-1 mg-1 protein) by hydrolysis of the His8-Leu9 bond and catabolism was inhibited by phosphoramidon (I50 approx. 10(-8) M), a specific inhibitor of endopeptidase-24.11. The same bond in GRP10 was cleaved by purified endopeptidase-24.11, and hydrolysis was equally sensitive to inhibition by phosphoramidon. SP was catabolized by gastric muscle peptidases (specific activity 1.7 nmol min-1 mg-1 protein) by hydrolysis of the Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 bonds, which is identical to the cleavage of SP by purified endopeptidase-24.11. The C-terminal cleavage of GRP10 and SP would inactivate the peptides. It is concluded that a membrane-bound peptidase in the stomach wall catabolizes and inactivates GRP10 and SP and that, in its specificity and sensitivity to phosphoramidon, this peptidase resembles endopeptidase-24.11.
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PMID:Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases. 241 13

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

Forty-two breast carcinomas were studied with different markers for detecting neuroendocrine differentiation. The Bodian and Grimelius silver stains were applied, as well as immunostaining for neurone specific enolase (NSE), chromogranin, prealbumin and a battery of hormones. All cases were studied by electron microscopy as well. The material included 29 infiltrating ductal carcinomas, 10 infiltrating lobular carcinomas and 3 tubular carcinomas. Immunostaining for hormones was obtained in 11 cases (gastrin and PP (4 cases each), leu-enkephalin (3 cases), substance P (2 cases), beta-endorphin (2 cases), ACTH (1 case) and bombesin (1 case). Three cases revealed immunostaining for more than one hormone. Sixteen cases were positively stained with rabbit anti-NSE (Dako Corporation) and included all the 11 cases with proven immunoreactivity for hormones. 20 cases were positively stained with sheep anti-NSE and only 8 of the 11 cases with immunoreactivity for hormones were included. Immunostaining for prealbumin was observed in only 1 case and chromogranin in only 5 cases. All cases were unstained with the Bodian stain, whereas 3 cases showed a positive argyrophilic reaction with the Grimelius technique. Ultrastructural studies revealed typical small membrane-bound electron dense granules in cytoplasm in 4 cases, all among the 11 cases with immunoreactivity for hormones. We conclude that immunostaining with rabbit anti-NSE is the best screening method for detecting breast carcinomas with neuroendocrine differentiation.
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PMID:A study of different markers for neuroendocrine differentiation in breast carcinomas. 243 99

Dual labeling electron microscopic immunocytochemistry was used to investigate the cellular substrate for functional interactions between substance P (SP) and dopamine in the rat nucleus accumbens. Coronal vibratome sections from acrolein-fixed brains were sequentially processed for the localization of: (1) a rat monoclonal antiserum against SP identified by the peroxidase--anti-peroxidase immunocytochemical method, and (2) a rabbit polyclonal antiserum against tyrosine hydroxylase (TH) identified by immunoautoradiography. The monoclonal rat antiserum recognized principally SP, but also exhibited cross-reactivity with certain other tachykinins such as substance K. Terminals showing SP-like immunoreactivity (SPLI) were 0.2-1.5 microns in diameter and contained numerous small (30-40 nm), round vesicles; one or more large (80-150 nm), dense-core vesicles; and an occasional membrane-bound multivesicular body. From a total of 114 SP-labeled terminals that were quantitatively analyzed, 30.1% formed symmetric synapses with dendrites; whereas only 8% formed asymmetric junctions with dendritic spines. Terminals showing SPLI also occasionally formed junctions with dendrites receiving synaptic input from other terminals that were similarly labeled for the peptide or from terminals immunoautoradiographically labeled for TH. In contrast to the low frequency of postsynaptic relationships, 39.8% of the terminals containing SPLI showed close associations with other unlabeled or TH-labeled terminal or preterminal axons. The axonic contacts were characterized by equally spaced membranes that were not separated by glial processes. Within the terminals containing SPLI, vesicles were located near the axonic contacts; whereas vesicles in unlabeled terminals were located more distally with respect to these appositions. We conclude that in the rat nucleus accumbens SP or a closely related tachykinin subserves principally inhibitory functions at postsynaptic sites as indicated by the prominence of symmetric junctions. The abundance of axonic associations and sparsity of convergent input from TH- and SP-labeled terminals at closely spaced sites on dendrites supports the concepts that a SP-like tachykinin also may modulate the release of dopamine through direct or indirect presynaptic mechanisms. The possibility that there may be more extensive postsynaptic associations through convergence at widely spaced sites on common neurons is discussed.
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PMID:Substance P in the rat nucleus accumbens: ultrastructural localization in axon terminals and their relation to dopaminergic afferents. 245 97

Substance P is a neuropeptide released in vivo from the substantia nigra, the principal substance P nerve terminal region in the rat brain. Its inactivation was investigated in a purified nigral synaptic membrane preparation. The membrane-bound enzyme shares many features with the endopeptidase 24-11 (EC 3.4.24.11): 1) hydrolysis of peptide bonds Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10, 2) sensitivity to the inhibition by phosphoramidon and 3) relative affinity for substance P. Bestatine and captopril inhibit only the hydrolysis of the metabolites. These results suggest that substance P is inactivated in substantia nigra by endopeptidase 24-11 and that a bestatin-sensitive aminopeptidase and angiotensin converting enzyme may play a role in subsequent degradation of the substance P metabolites.
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PMID:Metalloendopeptidase (EC 3.4.24.11) but not angiotensin converting enzyme is involved in the inactivation of substance P by synaptic membranes of the rat substantia nigra. 247 Oct 29

Ulex europaeus agglutinin I (UEA-I) is a plant lectin with an affinity for L-fucosyl residues in the chains of lactoseries oligosaccharides associated with medium- and smaller-diameter dorsal root ganglion neurons and their axonal processes. These enter Lissauer's tract and terminate within the superficial laminae of the spinal cord overlapping projections known to have a nociceptive function. This implies that the surface coatings of neuronal membranes may have a relationship with functional modalities. The present investigation further examined this concept by studying a neuronal projection with a nociceptive function to determine whether fucosyl-lactoseries residues were incorporated in its primary afferent terminals. Transganglionic transport of horseradish peroxidase (HRP) following injection into tooth pulp chambers was employed to demonstrate dental pulp terminals in the trigeminal spinal complex, while peroxidase and fluorescent tags were used concomitantly to stain for UEA-I. Double immunolabeling for substance P (SP) and gamma-aminobutyric acid (GABA) using peroxidase and colloidal gold allowed a comparison of the distribution of a known excitatory nociceptive transmitter with that of UEA-I binding in specific subnuclei. Synaptic interrelationships between UEA-I positive dental pulp primary afferent inputs and specific inhibitory terminals were also examined. SP immunoreactivity occurred in laminae I and outer lamina II (IIo) of subnucleus caudalis (Vc) and in the ventrolateral and lateral marginal region of the caudal half of subnucleus interpolaris (Vi), including the periobex area in which Vi is slightly overlapped on its lateral aspect by cellular elements of Vc. The adjacent interstitial nucleus (IN) also showed an intense immunoreactivity for this peptide antibody. UEA-I binding displayed a similar distribution pattern in both Vc and Vi, but extended into lamina IIi and the superficial part of Lamina III in Vc. Dental pulp terminals were found to have a comparable distribution; however, many extended into the dorsal portion of the caudal half of Vi and the ventromedial quadrant of rostral Vi. Electron-microscopic analysis showed that transganglionically labeled dental pulp terminals contained ovoid, complex membrane-bound vacuoles laden with transported HRP. The preterminal axon and synaptic membranes of those dental pulp terminals located in zones of Vc and Vi displaying an affinity for UEA-I were usually characterized by a patchy, electron-dense coating of the peroxidase tag. SP was demonstrated ultrastructurally with Protein-A colloidal gold (3-nm particles), whereas GABA immunoreactivity was revealed by the avidin-biotin-peroxidase method.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ulex europaeus agglutinin-I binding to dental primary afferent projections in the spinal trigeminal complex combined with double immunolabeling of substance P and GABA elements using peroxidase and colloidal gold. 247 97

The biologic activity of substance P has been demonstrated to be limited both in in vivo and in vitro by a membrane-bound protease, neutral endopeptidase (EC 3.4.24.11). The interaction of substance P with its receptor on guinea pig lung tissues was studied in the presence of an inhibitor of neutral endopeptidase under conditions that protect the peptide from degradation. Uptake of 0.1 nM [125I]-BH-substance P in lung membrane preparations was rapid at 4 degrees C, reaching equilibrium in 30 to 40 min, and binding was stable for at least 30 min thereafter. Binding was reversible and saturable. Scatchard analyses of saturation binding data are consistent with a single class of receptor molecules in both lung parenchymal and airway membranes, with a Kd of 2 to 3 nM and a receptor density of 4,000 to 5,000 fmol/g wet wt of tissue. In competitive binding experiments, neurokinin A and substance P methyl ester were equipotent and required approximately 100-fold higher concentrations to effect equivalent displacement than unlabeled substance P. Eledoisin also competed for [125I]-BH-substance P binding, but was less effective than the other analogs. The spasmogenically inactive derivative, substance P 1-9, did not compete for substance P binding at concentrations as high as 1 microM. Binding of [125I]-BH-substance P was rapidly and completely reversed by addition of 0.1 mM GTP, suggesting that association with a GTP binding protein is required for high affinity binding of substance P to its receptor in lung. The substance P receptor molecule was further characterized by covalently crosslinking [125I]-BH-substance P to membrane preparations followed by SDS-PAGE of the solubilized material.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the substance P receptor in guinea pig lung tissues. 248 20

Interaction of substance P with electrically neutral, planar lipid bilayers prepared from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and with anionic bilayers prepared from mixtures of 1,2-dioleoyl-sn-glycero-3-phosphocholine and brain phosphatidylserine was measured using the capacitance minimization method for monitoring the membrane surface potential caused by the positive charges and electric dipole moment of adsorbed peptide. Substance P bound to the electrically neutral bilayers from 9 mM KCl (buffered to pH 5.5 with 2.0 mM 2-(N-morpholino)ethanesulfonate) with a maximal binding density of about 1 x 10(-2) molecules per nm2 and a dissociation constant of about 2 x 10(-4) M. Measurement of the surface potential at different ionic strengths (shielding of surface charges) allowed distinction between the fixed-charge surface potential and a dipole potential. Ascribing this dipole potential to membrane-bound substance P would imply an effective dipole moment normal to the bilayer surface of about 20 Debye per molecule. Magnitude and polarity are consistent with an alpha-helical domain at the C-terminal end of substance P which is oriented normal to the surface of the membrane, and inserted so as to be inaccessible to the aqueous phase. Consistent measurements were obtained with anionic membranes at low substance P concentrations (10(-7)-10(-6) M; pH 7.2). They indicated electrostatic accumulation of the triply charged peptide on the surface of the membrane followed by hydrophobic interaction with the same parameters as for neutral membranes. The results agree with the membrane structure of substance P determined with infrared attenuated total reflection spectroscopy, circular dichroism measurements, and thermodynamic estimations.
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PMID:Reversible binding of substance P to artificial lipid membranes studied by capacitance minimization techniques. 248 29

Aminopeptidase M (EC 3.4.11.2), which can degrade low molecular weight opioid peptides, has been reported in both peripheral vasculature and in the CNS. Thus, we have studied the metabolism of opioid peptides by membrane-bound aminopeptidase M derived from cerebral microvessels of hog and rabbit. Both hog and rabbit microvessels were found to contain membrane-bound aminopeptidase M. At neutral pH, microvessels preferentially degraded low molecular weight opioid peptides by hydrolysis of the N-terminal Tyr1-Gly2 bond. Degradation was inhibited by amastatin (I50 = 0.2 microM) and bestatin (10 microM), but not by a number of other peptidase inhibitors including captopril and phosphoramidon. Rates of degradation were highest for the shorter peptides (Met5- and Leu5-enkephalin) whereas beta-endorphin was nearly completely resistant to N-terminal hydrolysis. Km values for the microvascular aminopeptidase also decreased significantly with increasing peptide length (Km = 91.3 +/- 4.9 and 28.9 +/- 3.5 microM for Met5-enkephalin and Met5-enkephalin-Arg6-Phe7, respectively). Peptides known to be present within or in close proximity to cerebral vessels (e.g., neurotensin and substance P) competitively inhibited enkephalin degradation (Ki = 20.4 +/- 2.5 and 7.9 +/- 1.6 microM, respectively). These data suggest that cerebral microvascular aminopeptidase M may play a role in vivo in modulating peptide-mediated local cerebral blood flow, and in preventing circulating enkephalins from crossing the blood-brain barrier.
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PMID:Metabolism of opioid peptides by cerebral microvascular aminopeptidase M. 287 69


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