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)

A reduction of striatal excitatory amino acids or of corticostriatal axons alters substance P (SP) and met5-enkephalin (ME) biosynthesis in striatal neurons of the rat. To determine the role of the N-methyl-D-aspartate (NMDA) receptor in this effect, adult rats were treated acutely with a single i.c.v. injection or chronically by 7 days of continuous infusion of an NMDA antagonist. The striatal content of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA was assessed by in situ hybridization histochemistry while the content of SP and ME in, respectively, the substantia nigra and globus pallidus was measured by quantitative radioimmunocytochemistry. Eight hours after a single injection, striatal PPT and PPE mRNA levels were significantly reduced. At 24 hr, the level of PPE had returned to control level whereas that of PPT mRNA remained depressed. Nigral SP and pallidal ME levels were not acutely changed. Chronically, the effect of NMDA antagonist at low doses was to increase the striatal content of PPE mRNA. However, at higher concentrations, the effect was to reduce in a dose-dependent manner the striatal content of PPT and PPE mRNA and the level of pallidal ME. The nigral level of SP did not change significantly at any dose. The results suggest that excitatory amino acid transmission mediated by the NMDA receptor serves as a tonic signal to stimulate neuroactive peptide biosynthesis.
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PMID:N-methyl-D-aspartate receptor antagonism alters substance P and met5-enkephalin biosynthesis in neurons of the rat striatum. 138 83

We investigated the effects of collagen II-induced arthritis on two cerebrospinal fluid (CSF) enzymes converting dynorphin A and substance P (SP), namely dynorphin-converting enzyme (DCE) and substance P endopeptidase (SPE). The products generated by these enzymes are the bioactive fragments Leu-enkephalin-Arg6 and substance P, respectively. The strain used (DA rats) is very sensitive towards induction of arthritis. The collagen arthritis is a chronic autoimmune arthritis induced by native rat collagen type II (CII). Following intradermal injection of CII into the tailbase. CSF was sampled on day 21 (acute arthritis) and day 38 (chronic arthritis). Control rats were untreated because the strain used developed an acute and self-limited arthritis (adjuvant arthritis) when administered vehicle (i.e. incomplete Freund's adjuvant). The DCE activity was significantly lowered in the acute phase of arthritis (P less than 0.05) when analysed with two-factor analysis of variance (ANOVA). The enzyme converting SP (SPE) also showed a significant decrease in the acute phase of arthritis (P less than 0.05). These results demonstrate that both DCE and SPE are affected in the acute phase of arthritis. A functional role of these enzymes in processing pain-related neuropeptides is therefore implicated.
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PMID:Decreased neuropeptide-converting enzyme activities in cerebrospinal fluid during acute but not chronic phases of collagen induced arthritis in rats. 138

The effects of dopamine-specific manipulations on neuropeptide gene expression in intrastriatal grafts of fetal striatal tissue were studied by quantitative in situ hybridization histochemistry, using 35S-labeled oligonucleotide probes. Messenger RNA transcripts for the striatal neuropeptides preproenkephalin (PPE) and preprotachykinin (PPT) were detected in neurons forming discrete patches in the striatal grafts. The relative abundance of PPE and PPT mRNA-expressing neurons within the graft patches (51-54%) was similar to that found in normal caudate-putamen. In specimens with intact dopamine afferents the expression of PPE mRNA in grafted neurons was similar to that found in normal caudate putamen, whereas the hybridization signal for PPT mRNA was 27% higher in the graft neurons than in the normal caudate-putamen. Removal of host dopaminergic afferents by 6-hydroxydopamine lesions of the ipsilateral mesostriatal dopamine pathway increased the hybridization signal for PPE mRNA both in the grafts (+84%) and in the spared ipsilateral host caudate-putamen (+125%), whereas the PPT signal was reduced by 53% in the grafts and by 51% in the remaining host caudate-putamen. Similarly, chronic treatment of grafted animals with the dopamine receptor antagonist haloperidol (2 mg/kg per day for 10 days) produced a 146% increase in the PPE signal in the grafts and a 175% increase in the intact contralateral caudate-putamen, whereas the signal for PPT mRNA was again decreased by 52% and 51% in the grafts and host caudate-putamen, respectively. These results show that the host nigrostriatal dopamine pathway differentially regulates enkephalin and substance P gene expression within striatal grafts and thereby exerts a tonic functional influence over grafted striatal neurons.
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PMID:Differential regulation of neuropeptide mRNA expression in intrastriatal striatal transplants by host dopaminergic afferents. 143 38

Thiol and aspartyl proteolytic activities in isolated secretory vesicles of neural (NL) and intermediate (IL) lobes of bovine pituitary were characterized with heterologous enkephalin and tachykinin precursor substrates, 35S-(Met)-preproenkephalin and 35S-(Met)-beta-preprotachykinin. IL and NL secretory vesicles contained thiol-dependent proteolytic activity that cleaved the enkephalin precursor with a pH optimum of 4.5; this activity resembled a novel "prohormone thiol protease' previously purified and characterized from adrenal medulla chromaffin granules. IL and NL vesicles also demonstrated aspartyl proteolytic activity with acidic pH optimum, as shown by pepstatin A inhibition of tachykinin and enkephalin precursor cleaving activity. This activity may be related to a previously characterized chromaffin granule aspartyl protease (CGAP) related to cathepsin D (2), as indicated by the presence of immunoreactive CGAP in NL secretory vesicles by anti-CGAP immunoblots. These results show that pituitary secretory vesicles, like chromaffin granules, may contain similar thiol-dependent and aspartyl proteolytic activities.
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PMID:Thiol and aspartyl proteolytic activities in secretory vesicles of bovine pituitary. 155 May 54

Purification and potential tachykinin and enkephalin precursor cleaving enzymes from bovine chromaffin granules was undertaken using as substrates the model precursors 35S-(Met)-beta-preprotachykinin [35S-(Met)-beta-PPT] and 35S-(Met)-preproenkephalin [35S-(Met)-PPE]. Purification by concanavalin A-Sepharose, Sephacryl S200, and chromatofocusing resulted in a chromaffin granule aspartyl protease (CGAP) that preferred the tachykinin over the enkephalin precursor. CGAP was composed of 47-, 30-, and 16.5-kDa polypeptides migrating as a single band in a nondenaturing electrophoretic gel system, and coeluting with an apparent molecular mass of 45-55 kDa by size-exclusion chromatography. These results suggest that two forms exist: a single 47-kDa polypeptide and a complex of 30 + 16.5-kDa-associated subunits. CGAP was optimally active at pH 5.0-5.5, indicating that it would be active within the acidic intragranular environment. Cleavage at basic residues was suggested by HPLC and HVE identification of 35S-(Met)-NKA-Gly-Lys as the major acid-soluble product generated from 35S-(Met)-beta-PPT. Neuropeptide K was cleaved at a Lys-Arg basic residue site, as determined by identification of proteolytic products by microsequencing and amino acid composition analyses. Structural studies showed that the three CGAP polypeptides were similar to bovine cathepsin D in NH2-terminal sequences and amino acid compositions, indicating that CGAP appears to be a cathepsin D-related protease or cathepsin D itself. The 47- and 16.5-kDa polypeptides of CGAP possessed identical NH2-terminal sequences, suggesting that the 16.5-kDa polypeptide may be derived from the 47-kDa form by proteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purification and characterization of a cathepsin D protease from bovine chromaffin granules. 156 70

CCAP (Crustacean Cardioactive Peptide), Proctolin, FMRFamide, Met- and Leu-enkephalin, Substance P, RPCH (red pigment concentrating hormone) and PDH (pigment dispersing hormone) were applied to the isolated retina of the crayfish Orconectes limosus. Changes in light sensitivity, measured as changes of the amplitude of the electroretinogram (ERG) were observed after application of RPCH, PDH and CCAP. RPCH caused an increase of the ERG amplitude to 133% of its reference value whereas PDH and CCAP decreased the amplitude to 78% and 30% respectively. A dose-response curve showed that 10(-9) mol/l CCAP produce a half-maximal effect.
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PMID:The effect of neuropeptides on the ERG of the crayfish Orconectes limosus. 159 Aug 91

Expression of the preprotachykinin (PPT) mRNA and of the preproenkephalin (PPE) mRNA in the rat striatum has been assessed by in situ hybridization. The results demonstrate that the PPT mRNA is regulated by glucocorticoids such that adrenalectomized (ADX) animals replaced with corticosterone for 5 days expressed higher levels of the mRNA than ADX animals. The corticosterone-induced increase in striatal PPT mRNA was evident after 16 h, but not after 2 h, of corticosterone treatment of ADX animals. Elevation of circulating corticosterone levels in intact rats by acute restraint stress, or by corticosterone injection did not change the level of PPT mRNA in the striatum. In intact rats there was a diurnal variation in the level of striatal PPE mRNA expression; adrenalectomy resulted in a decrease in the mRNA level and did not abolish the diurnal variation in expression. The level of PPT mRNA in the striatum was also decreased in response to ADX, but there were no significant diurnal changes in the expression of the PPT mRNA either in the intact or in the ADX animals.
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PMID:Glucocorticoid regulation of neuropeptide mRNAs in the rat striatum. 164 34

To investigate the functional relationship between the enteric nervous system and the intestinal neurotensin (N) cells, the release of neurotensin (NT) was measured upon vascular 8-min infusion periods of various neurotransmitters and neuropeptides in an isolated vascularly perfused rat jejunoileum. NT-like immunoreactivity (NT-LI) was measured with an antiserum that specifically recognizes intact NT. The cholinergic agonists methacholine and carbachol produced a strong release of NT-LI (250% and 700% of basal, respectively at 10(-5) M). The infusion of a lower dose (10(-7) M) was less effective in both cases. The nicotinic receptor agonist DMPP (10(-4) M) had no significant effect on NT-LI release. Norepinephrine (10(-6) M) produced a moderate and well-sustained secretion of NT (200% of basal). Infusion of higher doses of these neurotransmitters dramatically increased the arterial pressure. G-amino-n-butyric acid (GABA), histamine, serotonin and dopamine administered at final concentrations up to 10(-5) M had no effect on NT-LI release. In contrast, gastrin-releasing peptide and bombesin induced a dose-dependent transient increase of portal NT-LI (maximal value at 10(-7) M: 1000% of basal) followed by a rapid return to near basal values. Substance P (10(-7) M) evoked a prompt release of NT-LI with a peak at 600% of basal followed by a decline to 200% of basal at the end of the session. Leu-enkephalin and calcitonin-gene-related-peptide (CGRP, 10(-7) M) produced a small rise in portal NT-LI, while Met-enkephalin, dynorphin, vasoactive intestinal peptide (VIP), galanin, neuropeptide Y (NPY), peptide histidine isoleucine (PHI), neuromedin U and thyrotropin releasing hormone (TRH) had no stimulatory effect. Our results indicate that additionally to the secretion of NT induced by cholinergic agents and bombesin, substance P and to a lesser extent Leu-enkephalin are capable of stimulating NT release in the rat.
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PMID:Release of ileal neurotensin in the rat by neurotransmitters and neuropeptides. 167 14

This light microscopic immunohistochemical study investigates the distribution and target interrelations of nerve fibers in bronchus-associated lymphoid tissues (BALT) of rat and cat by using antisera against (1) the polyneuronal marker protein gene product 9.5 (PGP 9.5), (2) selected opioid and nonopioid peptides, and (3) the marker enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In both species, a similar distribution pattern of PGP, peptide, and catecholamine enzyme immunoreactive was observed. Anti-PGP 9.5 stained all nerve fibers (except some smaller, calcitonin gene-related peptide-immunoreactive (CGRP-ir) fibers presumably of the C-type) throughout the different compartments of BALT, e.g., under the epithelium, in the smooth muscle layer, along the vasculature, and between immune cells of BALT parenchyma. The distribution of fibers staining for peptides (substance P (SP), (CGRP), neuropeptide Y (NPY). Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu) and/or the catecholamine enzymes was also not compartment-specific. However, the density of the different peptidergic fibers and those staining for the marker enzymes exhibited region- and target-specific variations, e.g., fibers, cocontaining substance P and CGRP were more ubiquitous in nonvascular regions than codistributed NPY-, TH-, and DBH-ir fibers, which clearly prevailed in perivascular plexus. Regularly, nerve fibers staining for any of the peptides and markers investigated formed close contacts with mast cells, cells of the macrophage/monocyte cell line (identified as ED1 + cells), and/or other lymphoid cells, although with different frequencies. We assume that the SP/CGRP innervation is mainly of primary sensory origin, while the NPY innervation is chiefly derived from postganglionic noradrenergic sympathetic neurons. The VIP/PHI component is most likely postganglionic cholinergic while the opioid component, apparently derived from the Proenkephalin precursor, could be of differential origin. We propose that the neuroimmune connections in BALT play a significant role in the regulation and/or modulation of physiological/pathophysiological mechanisms of the lung. BALT may also be an integral part of the psycho-neuro-immune axis.
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PMID:The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers. 167 20

A membrane-bound enkephalin-degrading aminopeptidase was purified from the longitudinal muscle layer of the guinea pig small intestine by four steps of column chromatography using L-tyrosine beta-naphthylamide. The molecular weight of the enzyme was estimated to be 105,000 by gel filtration. The maximum activity was observed between pH 6.5 and 7.0. The Km value for leucine-enkephalin was 137 microM. The aminopeptidase activity toward aminoacyl beta-naphthylamide substrates was restricted to basic, neutral, and aromatic aminoacyl derivatives. No action was detected on acidic amino acid and proline derivatives. The enzyme was potently inhibited by the aminopeptidase inhibitors actinonin, amastatin, and bestatin, and bioactive peptides such as angiotensin III, substance P, and Met-Lys-bradykinin. The enzyme activity was also inhibited by the antibody against the purified serum enkephalin-degrading aminopeptidase of guinea pig at concentrations similar to those at which activity was observed toward serum enkephalin-degrading aminopeptidase and renal aminopeptidase M. The enzyme rapidly hydrolyzed Leu-enkephalin and Met-enkephalin with the sequential removal of the N-terminal amino acid residues. The enzyme also hydrolyzed two enkephalin derivatives, angiotensin III and neurokinin A. However, neurotensin, substance P, and bradykinin were not cleaved. These properties indicated that the membrane-bound enkephalin-degrading aminopeptidase in the longitudinal muscle layer of the small intestine is similar to the serum enkephalin-degrading aminopeptidase and resembles aminopeptidase M. It is therefore suggested to play an important role in the metabolism of some bioactive peptides including enkephalin in peripheral nervous systems in vivo.
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PMID:Enkephalin-degrading aminopeptidase in the longitudinal muscle layer of guinea pig small intestine: its properties and action on neuropeptides. 167 58


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