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)

Radioimmunoassays were developed for the tachykinins eledoisin (ELE) and kassinin (KAS) using antisera raised in rabbits. The antisera exhibited low (less than 0.1%) cross-reactivities to substance P (SP) and physalaemin (PHY), but crossreacted (with one exception, antiserum K7) to varying extents with neurokinin A (NKA) and neurokinin B (NKB). In the rat, the tissue distribution of the immunoreactive material detected by antiserum (E7) raised against ELE and by another antiserum (K1) raised against KAS both resembled that previously described for SP. Using the highly KAS-specific antiserum K7, no or only very low levels of immunoreactivity could be detected in extracts of various rat tissues. Gel permeation chromatography and ion-exchange chromatography of tissue extracts indicated that all antisera (except K7) detected the same population of immunoreactive molecules. One of the components was chromatographically indistinguishable from NKA. The tissue distribution of this component also resembled that of SP. Another immunoreactive component co-chromatographed with NKB at cation exchange chromatography. Acid tissue extracts, but not neutral tissue extracts, were found to contain immunoreactive components which appeared more basic than NKA and NKB. The total levels of immunoreactivity were higher in neutral than in acid tissue extracts. However, the ratio between the amounts of immunoreactivities in the two types of extracts varied considerably between tissues, indicating that tachykinin immunoreactive components may be present in different relative proportions in various tissues.
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PMID:Antisera raised against eledoisin and kassinin detect immunoreactive material in rat tissue extracts: tissue distribution and chromatographic characterization. 659 62

Cathepsin D was purified about 1000-fold from human brain cortex by a procedure involving ammonium sulfate fractionation (30-70%), Sephadex G-75 chromatography, affinity chromatography on pepstatin-Sepharose and isoelectric focusing. The enzyme was assayed fluorometrically at pH 3.2, the substrates used were globin or haemoglobin modified with pyridoxal-5'-phosphate. 6 multiple forms of cathepsin D were resolved in the isoelectric focusing step with pI values 4.4, 4.8, 5.3, 6.2, 6.5 and 6.8. Km of pyridoxal-globin and pyridoxal-haemoglobin for all 6 multiple forms is 1.8-2.0 X 10(-5) M and 1.3 to 4 X 10(-6) M, respectively, and Ki of pepstatin is 2-4 X 10(-9) M. Gel filtration of the multiple forms on Sephadex G-100 column showed that each has a molecular weight of about 50 000. Human brain cathepsin D has a pH optimum of 3.2 with a smaller second optimum at pH 4.0 (pyridoxal-haemoglobin being used as substrate). All the multiple forms have the same pH-dependence curve. On SDS-polyacrylamide gel electrophoresis the purified enzyme produced 3 bands approximately corresponding to Mr 50 000, 35 000 and 15 000. Study of the breakdown of substance P and its C-terminal heptapeptide by cathepsin D shows that cleavage occurs at the Phe-Phe linkages of both substrates tested.
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PMID:Cathepsin D from human brain: purification and multiple forms. 667 69

A porcine kidney microsomal metalloendopeptidase has been enriched 3900-fold. Gel filtration on a calibrated Toyo-Soda G-3000 SW column indicated an appropriate molecular weight for the endopeptidase of 88,000 +/- 2000. The purified enzyme is inhibited by a number of synthetic inhibitors of thermolysin. The endopeptidase hydrolyzes the succinyl (Suc)-containing fluorogenic peptide substrate Suc-Ala-Ala-Phe-(7-amino-4-methylcoumarin) at the Ala-Phe position with a Km of 2.9 X 10(-4) M. The endopeptidase also hydrolyzes a variety of peptides including corticotropin, substance P, angiotensin I and II, neurotensin, somatostatin, bradykinin, and the renin tetradecapeptide substrate. The endopeptidase hydrolyzes both [Leu]- and [Met]enkephalin at the Gly-Phe bond.
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PMID:Purification of a membrane-bound metalloendopeptidase from porcine kidney that degrades peptide hormones. 703 58

Physalaemin (Mr = 1284) is a potent undecapeptide from the skin of South American frogs. The amino acid sequence of the COOH-terminal region of this peptide is similar to that of substance P. An antiserum specific for the NH2-terminal sequence of physalaemin enabled the quantitation and localization of physalaemin-like immunoreactivity (PSLI) in mammalian tissues. PSLI is found in acid extracts of whole trachea from rat, rabbit, and guinea pig and in the tracheal mucosal layer in the dog, cow, and pig. The concentration determined by radioimmunoassay ranged from 1 to 15 ng/g dry weight of tissue, with rat trachea containing the highest amount. Gel filtration of an extract of rabbit trachea on Bio-Gel P-4 revealed a single peak of immunoreactivity that had an approximate Mr of 1700, similar to that detected in extracts of guinea pig and rabbit stomach. In contrast to amphibian physalaemin, mammalian PSLI 1) has a higher molecular weight, 2) is resistant to alpha-chymotrypsin or trypsin digestion, 3) elutes earlier from a C18 alkylsilane resin with increasing concentrations of methanol, and 4) can be separated from physalaemin by thin-layer chromatography. These data indicate that the mammalian PSLI is different in structure from the amphibian peptide.
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PMID:A substance with immunoreactivity to the peptide physalaemin in mammalian respiratory tissue. 716 58

Preprotachykinin B (PPT-B) contains two peptide sequences which are flanked by pairs of dibasic amino acids: the decapeptide neurokinin B and a 30 amino acid non-tachykinin peptide consisting of the amino acids 50-79 of PPT-B. Whereas the existence of neurokinin B is well established in brain and peripheral tissues, native PPT-B(50-79) has not been identified so far. We have previously studied the distribution of PPT-B(50-79)-immunoreactivity in the rat brain using antibodies directed against synthetic PPT-B(50-79). Now we adapted a radioimmunoassay for characterizing neurochemically PPT-B(50-79)-immunoreactivity in the rat. In the brain concentrations ranging from 2 to 180 fmol/mg wet tissue weight were measured using synthetic PPT-B(50-79) as standard. The highest concentrations were observed in the interpeduncular nucleus and in the hypothalamus (180 and 90 fmol/mg tissue, respectively). Intermediate concentrations (15 to 60 fmol/mg tissue) were present in cortical areas, in the hippocampus, the spinal cord and in the olfactory bulb. Modest levels were detected in the cerebellum. Considerably lower concentrations of PPT-B(50-79)-immunoreactivity were observed in peripheral tissues. They were highest in the adrenal medulla and in the urinary bladder (3.0 and 1.2 fmol/mg tissue, respectively). This distribution, as observed by radioimmunoassay, correlated to that previously revealed by immunocytochemistry. Tissue concentrations of total PPT-B(50-79) immunoreactivity, however, were slightly higher than those of neurokinin B. Gel filtration chromatography on Sephadex G50 and reversed phase HPLC revealed at least three PPT-B(50-79) immunoreactive peaks. About 90% of the PPT-B(50-79)-immunoreactivity was contained within 2 peaks of apparently higher molecular weight than PPT-B(50-79). A minor portion of PPT-B(50-79)-immunoreactivity comigrated with the synthetic peptide, suggesting that only minor amounts of PPT-B(50-79) are formed in vivo. The processing enzyme(s) cleaving protachykinin B at the pair of basic amino acids (Lys80-Arg81) located between PPT-B(50-79) and neurokinin B may not be acting at the Arg48-Arg49 site (followed by -Leu50) at the amino terminal end of PPT-B(50-79).
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PMID:Neurochemical characterization of preprotachykinin B(50-79) immunoreactivity in the rat. 765 92

Isolated parotid acinar cells embedded in Bio-Gel P-2 resin were perifused in small columns, and the effects of various agonists and their combinations on amylase release were studied. Isoproterenol gradually increased the rate of amylase secretion; its maximum response was attained about 5 min after the stimulation. A similar time course of changes in amylase secretion was elicited by dibutyryl cyclic AMP, forskolin and isobutylmethylxanthine. Carbachol (CCh) and substance P evoked biphasic stimulation of amylase secretion; an initial rapid and large peak and a following sustained plateau. The magnitude of the maximum response induced by CCh or substance P was almost the same as that induced by isoproterenol. In Ca2+-free medium, CCh evoked only the initial peak and did not produce the sustained plateau, but the effect of isoproterenol was little changed. Amylase secretion induced by isoproterenol, but not by CCh and substance P, was markedly decreased by lowering the temperature of the medium. Combined addition of isoproterenol and 1 microM CCh markedly augmented amylase secretion; the magnitude of its response was about three times that induced by isoproterenol alone. Potentiation was also observed between alpha- and beta-adrenergic receptors. Most of these results were very different from those obtained in batch systems. Thus, use of a perifusion system for analysis of amylase secretion is strongly recommended.
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PMID:Characteristics of amylase secretion induced by various secretagogues examined in perifused rat parotid acinar cells. 982 22

The trefoil factor TFF3 is a peptide predominantly produced by mucus-secreting cells in the small and large intestines. It has been implicated in intestinal protection and repair. The mechanisms that govern TFF3 secretion are poorly understood. The aim of this study was, therefore, to evaluate the influence of neurotransmitters, hormonal peptides and mediators of inflammation on the release of TFF3. For this purpose, an isolated vascularly perfused rat colon preparation was used. After a bolus administration of 1 ml isotonic saline into the lumen, TFF3 secretion was induced by a 30-min intra-arterial infusion of the compounds to be tested. TFF3 was evaluated in the luminal effluent using a newly developed radioimmunoassay. TFF3 was barely detected in crude luminal samples. In contrast, dithiothreitol (DTT) treatment of the effluent revealed TFF3 immunoreactivity, which amounted to about 0.3 pmol min(-1) cm(-1) in the basal state. Gel chromatography of DTT-treated luminal samples revealed a single peak that co-eluted with the monomeric form of TFF3. TFF3 was not detected in the portal effluent. Bethanechol (10(-6)-10(-4) M), vasoactive intestinal peptide (VIP, 10(-8)-10(-7) M) or bombesin (10(-8)-10(-7) M) induced a dose-dependent release of TFF3. In contrast, substance P evoked a modest release of TFF3, whereas calcitonin gene-related peptide (CGRP), somatostatin, neurotensin or peptide YY (PYY) did not modify TFF3 secretion. The degranulator compound bromolasalocid, 16,16-dimethyl PGE2 (dmPGE2) or interleukin-1-beta (IL-1-beta) also evoked a marked release of TFF3. In conclusion, TFF3 in the colonic effluent is present in a complex. This association presumably involves a disulfide bond. Additionally, the present results suggest a role for enteric nervous system and resident immune cells in mediation of colonic TFF3 secretion.
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PMID:Secretion of the trefoil factor TFF3 from the isolated vascularly perfused rat colon. 1149 77

The discovery of a potentially novel proline-specific peptidase from bovine serum is presented which is capable of cleaving the dipeptidyl peptidase IV (DPIV) substrate Gly-Pro-MCA. The enzyme was isolated and purified with the use of Phenyl Sepharose Hydrophobic Interaction, Sephacryl S-300 Gel Filtration, and Q-Sephacryl Anion Exchange, producing an overall purification factor of 257. SDS PAGE resulted in a monomeric molecular mass of 158kDa while size exclusion chromatography generated a native molecular mass of 328kDa. The enzyme remained active over a broad pH range with a distinct preference for a neutral pH range of 7-8.5. Chromatofocusing and isoelectric focusing (IEF) revealed the enzyme's isoelectric point to be 4.74. DPIV-like activity was not inhibited by serine protease inhibitors but was by the metallo-protease inhibitors, the phenanthrolines. The enzyme was also partially inhibited by bestatin. Substrate specificity studies proved that the enzyme is capable of sequential cleavage of bovine beta-Casomorphin and Substance P. The peptidase cleaved the standard DPIV substrate, Gly-Pro-MCA with a K(M) of 38.4 microM, while Lys-Pro-MCA was hydrolysed with a K(M) of 103 microM. The DPIV-like activity was specifically inhibited by both Diprotin A and B, non-competitively, generating a K(i) of 1.4 x 10(-4) M for both inhibitors. Ile-Thiazolidide and Ile-Pyrrolidide both inhibited competitively with an inhibition constant of 3.7 x 10(-7) and 7.5 x 10(-7) M, respectively. It is concluded that bovine serum DPIV-like activity share many biochemical properties with DPIV and DPIV-like enzymes but not exclusively, suggesting that the purified peptidase may play an important novel role in bioactive oligopeptide degradation.
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PMID:The purification and characterisation of novel dipeptidyl peptidase IV-like activity from bovine serum. 1510 72

Stromal cell-derived growth factor-1alpha (SDF-1alpha) is a member of the CXC chemokines and interacts with the G protein, seven-transmembrane CXCR4 receptor. SDF-1alpha acts as a chemoattractant for immune and hemopoietic cells. The Tac1 gene encodes peptides belonging to the tachykinin family with substance P being the predominant member. Both SDF-1alpha and Tac1 peptides are relevant hemopoietic regulators. This study investigated the effects of SDF-1alpha on Tac1 expression in the major hemopoietic supporting cells, the bone marrow stroma, and addresses the consequence to hemopoiesis. Reporter gene assays with the 5' flanking region of Tac1 showed a bell-shaped effect of SDF-1alpha on luciferase activity with 20 ng/ml SDF-1alpha acting as stimulator, whereas 50 and 100 ng/ml SDF-1alpha acted as inhibitors. Gel shift assays and transfection with wild-type and mutant IkappaB indicate NF-kappaB as a mediator in the repressive effects at 50 and 100 ng/ml SDF-1alpha. Northern analyses and ELISA showed correlations among reporter gene activities, mRNA (beta-preprotachykinin I), and protein levels for substance P. Of relevance is the novel finding by long-term culture-initiating cell assays that showed an indirect effect of SDF-1alpha on hemopoiesis through substance P production. The results also showed neurokinin 1 and not neurokinin 2 as the relevant receptor. Another crucial finding is that substance P does not regulate the production of SDF-1alpha in stroma. The studies indicate that SDF-1alpha levels above baseline production in bone marrow stroma induce the production of substance P to stimulate hemopoiesis. Substance P, however, does not act as autocrine stimulator to induce the production of SDF-1alpha. This study adds SDF-1alpha as a mediator within the neural-immune-hemopoietic axis.
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PMID:Stromal derived growth factor-1alpha: another mediator in neural-emerging immune system through Tac1 expression in bone marrow stromal cells. 1727 11

Topically applied morphine is routinely used to alleviate pain in cutaneous wounds such as burns and pressure sores. Evidence suggests the topical administration of exogenous opioid drugs may impair wound closure. This study examined the effects of topical morphine on a standardized model of cutaneous wound healing in the rat. Full-thickness 4mm diameter circular skin flaps were excised from the intrascapular region of male Sprague-Dawley rats. IntraSite Gel infused with either morphine-sulfate, neurokinin-1 (NK-1) or neurokinin-2 (NK-2) receptor antagonists, substance P (SP), neurokinin A (NKA), SP+morphine-sulfate, or NKA+morphine-sulfate was applied to the wound twice daily. Results demonstrated a significant overall delay in the time course of wound contraction in morphine-treated animals when compared with gel-only treated controls. The delay in wound contraction seen in morphine-treated animals increased in a concentration-dependent manner. Topical application of NK-1 or NK-2 receptor antagonists mimicked the effects of morphine in delaying wound closure, suggesting topical opioids impair wound closure via the inhibition of SP and NKA release peripherally into the healing wound. Additionally, no significant delays in closure were seen in rats receiving morphine combined with SP or NKA, demonstrating the ability of each neuropeptide to attenuate the effects of morphine in delaying wound closure and restore normal wound closure rates. The combination of SP or NKA and morphine-sulfate for wound therapy may provide local analgesia while maintaining normal closure rates.
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PMID:Delay of cutaneous wound closure by morphine via local blockade of peripheral tachykinin release. 1763 84


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