Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
 ...
PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.
 ...
PMID:UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms. 128 76

1. The effects of calcitonin gene-related peptide (CGRP) and other vasoactive mediators of inflammation on blood flow in the synovial vessels and plasma protein extravasation into the knee (femoro-tibial) joint of the pentobarbitone-anaesthetized rat were measured. 2. Changes in synovial blood flow were estimated by 133xenon clearance from the synovial cavity. CGRP (0.1 pmol and 10 pmol) and prostaglandin E1 (PGE1; 3 pmol and 300 pmol) significantly increased clearance from the knee joint measured 5 min after intra-articular injection. Substance P (10 pmol) had no effect on synovial blood flow. 3. Intra-articular perfusion of the rat knee with CGRP at concentrations up to 0.1 mM, or PGE1 at concentrations up to 10 microM, did not increase plasma extravasation into the synovial cavity measured by accumulation of intravenously injected 125I-albumin in the perfusate. 4. Plasma extravasation into the knee was significantly increased by infusion of bradykinin (0.1 microM), 5-hydroxytryptamine (1 microM) and histamine (0.1 mM), compared with the contralateral joints in the same animals which were perfused with Tyrode solution. 5. Perfusion of the knee joint with substance P did not specifically induce 125I-labelled albumin accumulation in the synovial cavity even at doses that had systemic effects as observed by marked plasma extravasation into other tissues. 6. The increase in plasma extravasation induced by histamine (0.1 mM) was potentiated by co-infusion with CGRP (0.1 microM) and PGE1 (3 microM). However the response to a submaximal dose (0.1 microM) of bradykinin, which induced similar plasma extravasation to histamine (0.1 mM), was not increased by co-infusion with CGRP or PGE1.7. These results show that CGRP is a potent vasodilator in the rat knee. CGRP released from sensory nerves may act synergistically with mediators of increased vascular permeability to modify the inflammatory response in this site.
 ...
PMID:Calcitonin gene-related peptide increases blood flow and potentiates plasma protein extravasation in the rat knee joint. 138 Mar 89

One of the major events involving inflammatory processes is the alteration of microcirculatory hemodynamics by inflammatory mediators released from tissue components. Using modern macrocirculatory techniques, 15 mu radioisotope labeled microspheres, 133Xe washout, laser Doppler flowmetry and double isotopes, 125 and 131I-albumin, and microcirculatory methods, intravital fluorescence microscopy with FITC labeled dextran, we have examined the effects of selected mediators, e.g. 5-hydroxytryptamine (5-HT), prostaglandin E2 (PG-E2), bradykinin (BK), substance P (SP), calcitonin gene related peptide (CGRP) and histamine on blood flow and vascular permeability in the pulp of experimental animals. Surprisingly, SP and CGRP caused weak albumin leakage in the pulp, while the opposite is true in high compliance tissues, such as muscles, suggesting that the vessels in a low compliance environment, such as the pulp, may not be as permeable in response to selected mediators. Intraarterial injection of 5-HT caused a strong vasoconstriction which was mediated by 5-HT1p receptor subtype. The pulpal 5-HT receptor subtype was identified by immunocytochemistry, receptor autoradiography and functional investigations. Intravital fluorescence microscopy observations of the rat incisor preparation showed that histamine, BK and PGE2 increased permeability, whereas isoproteranol caused partial inhibition of the BK-induced increase. In an induced pulpal inflammation model using plaque extract, blood flow increased over 40% in the moderately inflamed pulp, which demonstrated severe vasodilation and polymorpholeukocyte accumulation. In the partially necrotic pulp, blood flow decreased nearly 35%. Results of this study clearly show that there is a high structural/functional correlation in pulpal microcirculation in inflammation. As demonstrated in this presentation, the effects of inflammatory mediators on pulpal microcirculatory hemodynamics are complex.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of selected inflammatory mediators on blood flow and vascular permeability in the dental pulp. 150 95

We tested the hypothesis that exogenous substance P (SP) could enhance rat aortic permeability to plasma albumin. Fluorescein-labeled bovine serum albumin was used as the tracer. In vivo normalized albumin mass transfer rates (x10(-8) cm/sec) were 9.16 +/- 1.73, 14.20 +/- 2.76 (P less than 0.05) and 20.31 +/- 3.31 (P less than 0.001) for groups infused i.v. with 0.01 N acetic acid vehicle, 7.4 pmol and 0.74 pmol SP/kg/min for 5 min, respectively. No significant differences from the control group were found in rats receiving 150 pmol, 74 pmol nor 74 fmol SP/kg/min for 5 min. The results indicate that aortic permeability dynamics for plasma albumin can be enhanced by pmol levels of the tachykinin SP.
 ...
PMID:Substance P increases rat aortic albumin permeability. 169 12

Nasal permeability was studied in anaesthetized rats after topical challenge with methacholine (MC), substance P (SP), or capsaicin. The drugs were applied onto strips of filter paper. After drying, they were inserted into one side of the nasal cavity while the other side received strips without drugs. The filter paper strips were used not only to stimulate secretion but also to collect the resulting fluid. FITC-albumin was given i.v. and the amount appearing in the nasal fluid was captured on the strips and measured by fluorometry. The presence of FITC-albumin in nasal secretions reflects a leakage of plasma through the capillary endothelium and the nasal epithelium. MC, SP, and capsaicin stimulated the secretion of nasal fluid. SP and capsaicin, but not MC increased the concentration of FITC-albumin in the nasal fluid.
 ...
PMID:Nasal mucosal permeability after methacholine, substance P, and capsaicin challenge in the rat. 169 9

1. We have examined the effect of calcitonin gene-related peptide (CGRP) on basal mucus volume, lysozyme and albumin outputs from the ferret whole trachea in vitro, and on the outputs produced by methacholine and substance P (SP). We have also examined the effect of inhibiting neutral enkephalinase with thiorphan on the responses to CGRP. 2. CGRP (1-100 nM) produced small concentration-dependent increases in basal mucus volume, lysozyme and albumin outputs. These effect of CGRP were enhanced by thiorphan. The increases in basal outputs with CGRP and the potentiation by thiorphan were considerably less than previously observed with SP and neurokinin A (NKA). CGRP had no significant effect on potential difference (PD) across the trachea. 3. CGRP produced a concentration-dependent inhibition of methacholine- and SP-induced lysozyme output but a concentration-dependent increase in methacholine- and SP-induced albumin output. The effects of CGRP on methacholine-induced lysozyme and albumin outputs were enhanced by thiorphan. CGRP weakly inhibited methacholine-induced mucus volume output and weakly enhanced SP-induced mucus volume output. 4. Thus, CGRP weakly stimulates basal serous cell secretion and epithelial albumin transport, but does not alter epithelial integrity. CGRP inhibits the serous cell secretion due to methacholine or SP, but potentiates the epithelial albumin transport produced by these agents. The interaction between CGRP and other sensory neuropeptides or muscarinic agonists on airway submucosal glands and epithelium may be important in the normal airway and in inflammatory airway diseases where release of sensory neuropeptides is enhanced.
 ...
PMID:The effects of calcitonin gene-related peptide on submucosal gland secretion and epithelial albumin transport in the ferret trachea in vitro. 171 May 27

The sources of different chemical substances in the NF of allergic patient, such as albumin, secretory IgA, histamine, leukotriene, kinin and substance P were investigated. To accomplish this, we challenged the inferior turbinate on one side, but separately collected NF from both sides in patients with nasal allergy to house-dust. Provocation was done with paper disc containing dried allergen extract. Collection was done by suction for the first five minutes immediately after the onset of a positive response to nasal provocation. The total amount of the chemical substances on each side was analyzed separately and compared. Significant differences were seen between both sides only for histamine and leukotriene. In consideration with the previous reports, it is suggested that in nasal allergen challenge the major sources are glandular secretion for secretory IgA, and albumin, and secretion for migrating cells for histamine and leukotriene. The major sources responsible for kinin and substance P, however, are not defined.
 ...
PMID:The sources of chemical substances in allergic nasal fluid. 171 74

Our purpose was to characterize the tachykinin receptor type involved in nasal obstruction to exogenous substance P in rhinitic patients. We also attempted to assess biochemical and cellular events associated with this response. Nasal challenges were performed in seven patients with allergic rhinitis. They received increasing doses (10 to 80 nmol) of substance P, of neurokinin A, of the N-terminal fragment of substance P, substance P(1-9), and of saline on 4 different days separated by 14 days. Nasal airway resistance (NAR) increased in a dose-dependent manner on substance P. Maximal increase reached 4.5-fold basal NAR. Response to neurokinin A was significantly lower (less than 2-fold basal NAR). No effect was observed on substance P(1-9) and saline. This order of activity [substance P much greater than neurokinin A greater than substance P(1-9) = saline] indicates an NK1 receptor-mediated mechanism inducing local vasodilation. No histamine release was found after any of the four challenges. Proteins significantly increased in nasal lavage fluid on both substance P and neurokinin A, whereas substance P(1-9) and saline had no effect. The percentage of albumin increased in nasal lavage fluid from 30 to 50% of total proteins on substance P and neurokinin A, indicating microvascular leakage. Polymorphonuclear cells significantly increased from 9 to 36% on substance P, from 13 to 49% on neurokinin A, and from 13 to 55% on substance P(1-9). Eosinophils increased in five patients on substance P (from 0.1 to 5% for the group), in three patients after neurokinin A, and in two after substance P(1-9).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical and inflammatory responses to exogenous tachykinins in allergic rhinitis. 171 29

ACE-inhibitors have for some time been used in the treatment of hypertension. Apart from inhibiting the conversion of angiotensin I to II, the drugs also affect the metabolism of some inflammatory agents, like bradykinin and substance P. Egg albumin (EA)-sensitized guinea pigs were pretreated with the ACE-inhibitors. Measurement of flare and wheal areas induced by an intradermal injection of EA, showed that enalaprilat significantly increased, whereas cilazaprilat slightly decreased, the reaction area. Enalaprilat also showed an enhancement in histamine and substance P (SP) contents in the skin. In vitro incubation of guinea pig biopsies with enalaprilat potentiated EA- but not SP-induced histamine release. The EA-induced effect was abolished if the animals were pretreated with capsaicin. The conclusion is that cilazaprilat, in contrast to enalaprilat, does not potentiate inflammatory reactions in the guinea pig.
 ...
PMID:Enalaprilat versus cilazaprilat: a comparison of allergic skin reactions in the guinea pig. 171 46


1 2 3 4 5 6 7 8 9 Next >>