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)

Immunohistochemical techniques were used to study the adrenal organs of the anuran species Rana esculenta, Caldula pulchra and Bufo marinus with respect to the distribution and coexistence of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), Leu-enkephalin (Leu-ENK). Met-enkephalin-Arg-Phe (MEAP) and dynorphin A 1-17 (DYN). Antisera against enzymes involved in catecholamine synthesis, i.e., dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), were used for the identification of chromaffin cells. ANP-immunoreactive (-IR) cells occurred in high densities (30%-70% of the total cell population) in all species investigated. In C. pulchra and B. marinus, BNP-IR cells constituted a population of non-DBH-IR and non-TH-IR cells that were different from the ANP-IR cells. A large proportion of the adrenal cells (10%-55%) were immunoreactive to Leu-ENK, and a minority (2%-5%) showed MEAP-immunoreactivity. DYN-immunoreactivity was not observed. The anurans studied exhibited small numbers of SP-IR, CGRP-IR and NPY-IR cells. Immunoreactivities for ANP + Leu-ENK and Leu-ENK + MEAP were shown to coexist. In C. pulchra and B. marinus, immunoreactions for ANP + NPY, ANP+SP and SP + CGRP were also colocalized. Except for DYN, all neurohormonal peptides also occurred in intra-adrenal nerve fibers. SP-IR fibers also displayed CGRP-immunoreactivity and some Leu-ENK-IR fibers contained MEAP-immunoreactivity. In C. pulchra, NPY-IR fibers were found that also showed ANP-immunoreactivity.
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PMID:Distribution patterns and coexistence of neurohormonal peptides (ANP, BNP, NPY, SP, CGRP, enkephalins) in chromaffin cells and nerve fibers of the anuran adrenal organ. 137 3

A number of different neuroactive substances have been found in striatal projection neurons and in fibers and terminals in their target areas, including substance P (SP), enkephalin (ENK), and dynorphin (DYN). In a preliminary report on birds and reptiles, we have suggested that SP and DYN are to a large extent found in the same striatal projection neurons and that ENK is found in a separate population of striatal projection neurons. In the present study, we have examined this issue in more detail in pigeons and turtles. Further, we have also explored this issue in rats to determine whether this is a phylogenetically conserved feature of basal ganglia organization. Simultaneous immunofluorescence double-labeling procedures were employed to explore the colocalization of SP and DYN, SP and ENK, and ENK and DYN in striatal neurons and in striatal, nigral, and pallidal fibers in pigeons, turtles, and rats. To guard against possible cross-reactivity of DYN and ENK antisera with each others' antigens, separate double-label studies were carried out with several different antisera that were specific for DYN peptides (e.g., dynorphin A 1-17, dynorphin B, leumorphin) or ENK peptides (leucine-enkephalin, metenkephalin-arg6-gly7-leu8, methionine-enkephalin-arg6-phe7). The results showed that SP and DYN co-occur extensively in specific populations of striatal projection neurons, whereas ENK typically is present in different populations of striatal projection neurons. In pigeons, 95-99% of all striatal neurons containing DYN were found to contain SP and vice versa. In contrast, only 1-3% of the SP+ striatal neurons and no DYN neurons contained ENK. Similarly, in turtles, greater than 75% of the SP+ neurons were DYN+ and vice versa, whereas ENK was observed in fewer than 5% of the SP+ neurons and 2% of the DYN+ neurons. Finally, in rats, more than 70% of the SP+ neurons contained DYN and vice versa, but ENK was found in only 5% of the SP+ neurons and in none of the DYN+ perikarya. Fiber double-labeling in the striatum and its target areas (the pallidum and substantia nigra) was also consonant with these observations in pigeons, turtles, and rats. These results, in conjunction with studies in cats by M.-J. Besson, A.M. Graybiel, and B. Quinn (1986; Soc Neurosci. Abs. 12:876) strongly indicate that the co-occurrence of SP and DYN in large numbers of striatonigral and striatopallidal projection neurons in a phylogenetically widespread, and therefore evolutionarily conserved, feature of basal ganglia organization.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extensive co-occurrence of substance P and dynorphin in striatal projection neurons: an evolutionarily conserved feature of basal ganglia organization. 169 32

Three peptide neuromodulators that are found in high concentration in the substantia nigra: dynorphin A 1-8, met5-enkephalin-arg6-gly7-leu8 and substance P, were measured by specific radioimmunoassays in nigral tissue from normals and schizophrenics postmortem. Substance P and dynorphin were unchanged between the two groups. However, the proenkephalin-derived peptide was significantly elevated in the schizophrenic group. The immunoreactivity was identified as authentic met5-enkephalin-arg6-gly7-leu8 by high pressure liquid chromatography. The data suggest that a different set of regulatory controls exists for nigral enkephalin peptides as compared to dynorphin and substance P, and that the former system may be disordered in schizophrenia.
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PMID:Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients. 170 47

1. The effects of neuropeptide Y (NPY) and a range of C terminal fragments were investigated both on basal short circuit current (s.c.c.) and electrical field stimulated responses in voltage clamped preparations in rat jejunal mucosa. 2. Most of the NPY fragments tested had direct effects upon the mucosa, reducing baseline s.c.c. with EC50 values of 1 micron or more. NPY was 30 times more effective than any of the fragments tested and the order of potency was: NPY much greater than NPY (11-36) greater than or equal to (12-36) greater than or equal to (13-36) greater than or equal to (14-36). NPY (15-36), (16-36), (20-36) and (22-36) were still less effective and complete concentration-response curves could not be constructed. NPY (26-36), des amido NPY and the C-terminal flanking peptide of NPY (CPON) were all inactive and did not significantly alter responses to NPY. 3. Electrical field stimulation (EFS) of mucosal preparations elicited rapid transient secretory responses in the presence of hexamethonium and atropine. NPY and fragments attenuated these secretory responses and where concentration-response relationships could be compared at a given time point the following order of potency was obtained: NPY much greater than NPY (11-36) greater than NPY (13-36). Again NPY (26-36), des amido NPY and CPON were ineffective, while at single concentrations (300 nM) a graded attenuation of EFS responses was obtained with NPY (14-36) greater than or equal to NPY (15-36) greater than NPY (16-36) greater than or equal to NPY (20-36) greater than NPY (22-36). 4. The attenuation of EFS responses by these peptides was not dependent upon the basal secretory state. Pretreatment of tissues with piroxicam reduced s.c.c. and attenuated further reductions in s.c.c. by NPY, but had no effect upon NPY-mediated inhibition of electrically-stimulated secretory responses. 5. NPY fragments attenuated both basal and EFS generated secretion. Since fragments are effective these receptors must, by definition be Y2-like. NPY (11-36) and NPY (13-36) at 300nm and 1 microM did not significantly attenuate secretory responses to either carbachol (CCh) or substance P (SP). A 1 microM concentration of either fragment was equivalent in effect to 30nm NPY upon basal current, but NPY at this concentration significantly reduced both CCh- and SP-induced secretion. The reduced spectrum of fragment activity together with the different order and potency ratios obtained with these three peptides indicates a presynaptic action for NPY and the fragments.
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PMID:The effects of neuropeptide Y and its fragments upon basal and electrically stimulated ion secretion in rat jejunum mucosa. 225 32

In this study we sought to establish the distribution, projections and neurochemical coding of opioid immunoreactive neurons in secretomotor pathways of the guinea-pig ileum. Non-cholinergic secretomotor neurons in the submucous ganglia have been shown to be immunoreactive for dynorphin A 1-8, dynorphin A 1-17, dynorphin B and alpha neo-endorphin while cholinergic neurons have been shown to be immunoreactive for dynorphin A 1-8 only. Thus all submucous neurons in the guinea-pig ileum are immunoreactive for prodynorphin-derived peptides. Two major populations of opioid immunoreactive fibres projecting to the submucous ganglia have been established. Firstly, neurons immunoreactive for prodynorphin-derived peptides and vasoactive intestinal peptide project anally from the myenteric plexus to the submucous ganglia. Secondly, a substantial proportion of sympathetic postganglionic fibres immunoreactive for tyrosine hydroxylase, and projecting from the coeliac ganglion to submucous ganglia, have been shown to be immunoreactive for prodynorphin-derived peptides. Other smaller populations of opioid-immunoreactive neurons include fibres immunoreactive for substance P, enkephalin and dynorphin A 1-8 which project from the myenteric plexus to the non-ganglionated plexus of the submucosa. These fibres are probably excitatory motor neurons to the muscularis mucosae. The present paper has described several distinct populations of opioid immunoreactive neurons in secretomotor pathways of the guinea-pig ileum. Furthermore we have shown that these enteric or postganglionic sympathetic neurons contain opioid peptides in combination with other neurotransmitter substances. These results should provide a firmer basis on which to plan functional experiments to elucidate the physiological role of opioid peptides in the enteric nervous system.
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PMID:Opioid-like immunoreactive neurons in secretomotor pathways of the guinea-pig ileum. 227 Jan 43

While several peptides have been shown to coexist in perikarya within dorsal root ganglia of rat, coexistence of peptides has not been confirmed in axons associated with these neurons. In this study, the coexistence of substance P (SP) with somatostatin (SOM), calcitonin gene-related peptide (CGRP), dynorphin A 1-8 (DYN), neurotensin (NT), galanin (GAL), and 5-HT in varicosities was visualized using fluorescence immunohistochemistry. Densities of immunoreactive varicosities within laminae I and II of the dorsal horn of the rat spinal cord were quantified by computer-assisted image analysis. Decreases in densities of immunoreactive varicosities as a result of multiple unilateral dorsal rhizotomies were used to determine proportions of immunoreactive varicosities associated with primary afferent neurons. Three observations were made. (1) Dorsal rhizotomy depleted greater than one-third of the varicosities individually immunoreactive for SP, SOM, GAL, or DYN, confirming the association of these peptides with primary afferent neurons. (2) SP coexisted with CGRP, GAL, and DYN in varicosities within the dorsal horn of normal animals. (3) CGRP-, SP+CGRP-, and SP+GAL-immunoreactive varicosities were nearly depleted following dorsal rhizotomy. The depletion of these peptides, particularly in combination, indicates that they may be used as markers for varicosities of some primary afferent neurons within the superficial laminae of the dorsal horn of the rat spinal cord.
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PMID:A quantitative study of the coexistence of peptides in varicosities within the superficial laminae of the dorsal horn of the rat spinal cord. 264 83

A metalloendopeptidase (MEP) isolated from rabbit liver microsomes with substrate specificity for peptides containing Arg at the P1 and P4 positions has recently proved to be identical to soluble angiotensin-binding protein present in the cytosol. Here we describe the peptide-degrading specificity of MEP, determined using various bioactive peptides and novel fluorogenic substrates for the enzyme. MEP degraded oligopeptides, including bradykinin, alpha-neoendorphin, bovine adrenal medulla dodecapeptide, substance P, bombesin, neurotensin, and alpha-endorphin, but not polypeptides such as reduced lysozyme and histone H4, hence, MEP probably belongs to the family of endo-oligopeptidases. It cleaved most preferentially at the -Phe-Ser- bond of bradykinin (kcat/Km = 2.8 x 10(4) M-1.S-1) but did not cleave high molecular weight and low molecular weight kininogens, the precursors of bradykinin. MEP did not cleave angiotensin I, dynorphin A 1-13, somatostatin, and luteinizing hormone-releasing hormone, some of which are good substrates for metalloendopeptidase-24.15, metalloendopeptidase-24.16, N-arginine dibasic convertase, and yeast endopeptidase-24.15 related peptidase. An active site-directed inhibitor of metalloendopeptidase-24.15, N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate also had no effects on the amidolytic activity of MEP. Based on the cleavage sites of bioactive peptides and processing sites of vitamin K-dependent proproteins, intramolecularly quenched fluorogenic peptide substrates were newly synthesized. Among the thirteen substrates used, the most reactive was 2-aminobenzoyl-Ala-Arg-Val-Arg-Arg-Ala- Asn-Ser-2,4-dinitroanilinoethylamide (kcat/Km = 9.3 x 10(5) M-1.S-1). An angiotensin antagonist, [Sar1, Ala8]-angiotensin II, inhibited hydrolysis of the substrate by MEP in a competitive manner (Kl = 7.6 microM). MEP cleaved oligopeptides even on the carboxyl side of proline residue and these peptides are resistant to hydrolysis by the cytosol-derived proteasome, therefore MEP may participate in the catabolism of oligopeptides in the cytosol, together with other endo-oligopeptidases.
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PMID:Substrate specificity of rabbit liver metalloendopeptidase and its new fluorogenic peptide substrates. 857 4

Although the tachykinins substance P (SP) and neurokinin A have been largely localized to neurons, eosinophils have also been shown to express these peptides. Our aim was to determine whether rat alveolar macrophages (AM) express preprotachykinin gene-I (PPT-I) mRNA that encodes these tachykinins and to examine expression during inflammation. PPT-I mRNA was detected by reverse transcription (RT)-polymerase chain reaction (PCR) in AM and brain (control) but not in peritoneal macrophages. Northern analysis showed that PPT-I mRNA was induced two- to fourfold by in vivo treatment of rats with intratracheal lipopolysaccharide (LPS) and in vitro after 4 h of exposure to LPS. This increase was inhibited by dexamethasone. In situ RT-PCR and immunocytochemistry further confirmed that AM express PPT-I mRNA and SP-like immunoreactivity, respectively, which was enhanced by LPS treatment. A 1.3-kb transcript consistent with PPT-I mRNA was detected by Northern analysis of bronchoalveolar lavage neutrophils. Therefore, rat AM express PPT-I mRNA that is upregulated in AM by LPS and is attenuated by dexamethasone. PPT-I mRNA was also detected in lung neutrophils.
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PMID:Rat alveolar macrophages express preprotachykinin gene-I mRNA-encoding tachykinins. 937 37

We examined the effects of adenosine and its analogues on vascular permeability in rat trachea using Evans blue dye as a marker for plasma leakage. Inhalation of N6-2-(4-aminophenyl) ethyladenosine (APNEA), a specific A 3 receptor agonist, increased microvascular leakage in a dose-dependent manner, but adenosine, [R]-N6-(1-Methyl-2-phenylethyl) adenosine (R-PIA), aspecific A 1 receptor agonist, and 5'-(N-ethyl-carboxamide) adenosine (NECA), a specific A 2 receptor agonist, had no effect. Inhalation of capsaicin increased vascular permeability in a dose-dependent manner. Pretreatment with NECA (10-1000 nmol/kg, i.v.) but not adenosine (100 nmol/kg i.v.), R-PIA (100 nmol/kg, i.v.) or APNEA (100 nmol/kg, i.v.) inhibited microvascular leakage produced by capsaicin aerosol (3 x 10(-5) M) in a dose-dependent manner. However, NECA (10-100 nmol/kg, i.v.) failed to inhibit substance P aerosol (10(-4) M)-induced extravasation of the dye. These findings suggest that stimulation of adenosine A 3 receptors produces airway vascular permeability, and that A 2 receptors inhibit neurogenic plasma extravasation, presumably by inhibiting the release of tachykinins from sensory nerves.
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PMID:[Effect of adenosine and its analogues on microvascular leakage in the rat trachea]. 965 68

Peptides structurally related to mammalian tachykinins have recently been isolated from the brain and intestine of several insect species, where they are believed to function as both neuromodulators and hormones. Further evidence for the signaling role of insect tachykinin-related peptides was provided by the cloning and characterization of cDNAs for two tachykinin receptors from Drosophila melanogaster. However, no endogenous ligand has been isolated for the Drosophila tachykinin receptors to date. Analysis of the Drosophila genome allowed us to identify a putative tachykinin-related peptide prohormone (prepro-DTK) gene. A 1.5-kilobase pair cDNA amplified from a Drosophila head cDNA library contained an 870-base pair open reading frame, which encodes five novel Drosophila tachykinin-related peptides (called DTK peptides) with conserved C-terminal FXGXR-amide motifs common to other insect tachykinin-related peptides. The tachykinin-related peptide prohormone gene (Dtk) is both expressed and post-translationally processed in larval and adult midgut endocrine cells and in the central nervous system, with midgut expression starting at stage 17 of embryogenesis. The predicted Drosophila tachykinin peptides have potent stimulatory effects on the contractions of insect gut. These data provide additional evidence for the conservation of both the structure and function of the tachykinin peptides in the brain and gut during the course of evolution.
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PMID:Expression and functional characterization of a Drosophila neuropeptide precursor with homology to mammalian preprotachykinin A. 1080 63


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