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)

Stimulation of sensory nerves in the airway mucosa of the rat evokes the release of inflammatory peptides such as substance P, which can increase microvascular permeability, resulting in a phenomenon known as neurogenic plasma extravasation. The change in vascular permeability is mediated by NK-1 receptors and is caused by the formation of gaps between endothelial cells of postcapillary venules and small collecting venules, which are the same vessels as are affected by inflammatory mediators such as histamine and bradykinin. Respiratory tract infections caused by Sendai virus or Mycoplasma pulmonis can intensify neurogenic plasma extravasation in the airway mucosa, as indicated by the amount of microvascular leakage evoked by substance P or capsaicin. M. pulmonis infections can produce a 30-fold increase in the magnitude of neurogenic plasma extravasation, which is evident 4 wk after infection and may be permanent. A proliferation of venules in the airway mucosa and heightened sensitivity of these vessels to inflammatory mediators are key elements of the increase in plasma extravasation. Exposure of M. pulmonis-infected rats to ammonia exacerbates the infections and further augments the responsiveness of mucosal venules to inflammatory mediators. Despite this increased responsiveness, the vessels are not abnormally leaky in the absence of inflammatory stimuli. These findings emphasize the importance of airway infections as factors that can cause a potent, long-lasting increase in the sensitivity of the microvasculature of the airway mucosa to inflammatory mediators.
 ...
PMID:Infections intensify neurogenic plasma extravasation in the airway mucosa. 144 6

Substance P (SP) is one of the endogenous tachykinin peptides implicated in neurogenic inflammation and may be critically involved in diseases as diverse as asthma, arthritis and inflammatory bowel disease. The current study was initiated to identify a rich source of SP receptor that would be amenable for studying the regulatory mechanism of the receptor. By using a radioligand receptor binding technique, sheep ileal smooth muscle membranes showed a much higher density of [3H]SP specific binding than other non-neural rat or sheep tissues and organs surveyed. Of the protease inhibitors tested, only phosphoramidon, a specific and potent enkephalinase inhibitor, prevented the degradation of [3H]SP and enhanced [3H]SP binding to the membrane. [3H]SP binding to the specific binding sites in the membranes was time-dependent and reached a steady state after 60 min at 22 degrees C in 25 mM Tris.NH3 (pH 7.4). Calcium and magnesium ions enhanced [3H]SP specific binding. Saturation binding studies showed that the dissociation constant (KD) and the density of maximum binding sites for [3H]SP specific binding were 0.54 nM and 83 fmol/mg of protein, respectively. The specificity of the [3H]SP labeled sites was SP greater than (4-11) SP greater than eledoisin greater than spantide greater than neurokinin-A greater than D-Pro2D-Phe7D-Trp9-SP. Neurokinin-B and senktide showed no inhibition of [3H]SP binding.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Identification and characterization of the substance P receptor in sheep intestinal smooth muscle membranes. 169 67

Porcine calpains (Ca2+-dependent cysteine proteinases) I and II, which had been purified each to a homogeneous state, were found to hydrolyze specifically carboxyl-terminal amide of substance P and several other biologically active peptidyl amides. This amidase-like activity was demonstrated both by determining released ammonia and by separating products on high-performance liquid chromatography followed by amino acid analysis. The calpain-catalyzed deamidation of substance P occurred exclusively at the carboxyl-terminal amide, leaving the side-chain glutamine intact. Enkepharinamide and MSH-release inhibiting factor were scarcely deamidated. Calpains I and II showed similar specificities for these amide substances and similar profiles of inhibitions by various protease inhibitors, but distinctly different Ca2+ requirements. The specificity constants, kcat/Km, for substance P were found to be three to four orders of magnitude higher than those for the synthetic substrates.
 ...
PMID:Amidase-like activity of calpain I and calpain II on substance P and its related peptides. 241 62

The neuropeptide substance P (SP) released from airway sensory C fibers accelerates mucociliary activity, and C fibers in the airways are stimulated by various irritants including ammonia (NH3) vapor. The short-term effects of NH3 vapor on mucociliary function in the in the maxillary sinus of rabbits anesthetized with urethane were investigated by a photoelectric technique. Challenges with 1.5 ml NH3 increased mucociliary activity dose-dependently, the maximal response being 26.6 +/- 1.6%. The increase appeared within 1.3 +/- 0.3 s after exposure. Atropine and hexamethonium decreased the effect of NH3, indicating that part of the response was mediated by cholinergic effector neurons, but a noncholinergic effect clearly remained. Pretreatment with large doses of capsaicin (13 mg i.a.) abolished the response, whereas the SP antagonist (D-Pro2, D-Trp7,9) SP inhibited the noncholinergic response. Challenges with NH3 vapor also decreased the respiratory rate. An identical response was noticed during injections with the C fiber stimulant capsaicin. Together these results indicate that NH3 vapor triggers a mucociliary protective reflex in the airways, involving capsaicin-sensitive C fibers. The recorded increase of mucociliary activity is probably due to the combined effect on the mucociliary system of both SP and acetylcholine released from the afferent and efferent part of the reflex arc, respectively.
 ...
PMID:Stimulation of C fibers by ammonia vapor triggers mucociliary defense reflex. 357 9

We investigated the effects of the substance P (SP) blocker [D-Pro2,D-Trp7,9]-SP on the response of rapidly adapting pulmonary stretch receptors (RARs) to SP administered into the right atrium, or ammonia vapor inhaled into the lungs in anesthetized, spontaneously breathing rabbits. Right atrial administration of SP (0.3, 1.0, and 3.0 micrograms/kg) caused an increase in the RAR activity, and this increase became more prominent as the dose of SP was increased. The RARs increased their activity following inhalation of vapor from 5 and 10% ammonia solutions, and the increase was concentration dependent. The excitatory responses of RAR activity to SP at different doses were greatly diminished or completely blocked by administration of the selective SP antagonist (300 and 500 micrograms/kg). However, the ammonia-induced RAR stimulation was not significantly altered by prior treatment with the SP blocker (300 and 500 micrograms/kg). These results suggest that the stimulation of RARs by ammonia does not occur as a result of the release of SP from sensory nerves in the airways and lungs.
 ...
PMID:Substance P antagonist does not block the stimulation of rapidly adapting pulmonary stretch receptors by ammonia. 750 41

This study was conducted to test the hypothesis that L-glutamine has differential effects on nitric oxide (NO) synthesis from L-arginine in bovine venular endothelial cells (EC) stimulated by A23187 (a Ca++ ionophore) and receptor-mediated vasodilators (bradykinin and substance P). EC were cultured at 37 degrees C for 24 h in the presence of 0.4 mM L-arginine and 0.0 to 2.0 mM L-glutamine with or without 1 microM A23187, 1 microM bradykinin or 10 microM substance P. The release of nitrite and nitrate by EC was used as an indicator of NO synthesis. A23187, bradykinin or substance P increased NO synthesis from L-arginine by EC in the presence or absence of L-glutamine. The addition of L-glutamine (0.5 and 2 mM) markedly increased intracellular concentrations of L-glutamine, L-glutamate and L-aspartate and decreased NO synthesis by EC in a concentration-dependent manner in the presence or absence of A23187, bradykinin or substance P. L-Glutamine had no effect on L-arginine uptake by EC or on intracellular L-arginine concentration. Neither L-glutamine nor its glutaminase metabolites (ammonia, L-glutamate and L-aspartate) had any effect on endothelial NO synthase activity. Taken together, these results suggest that the inhibition by L-glutamine of NO synthesis from L-arginine is unlikely to result from an effect of L-glutamine on L-arginine transport or NO synthase activity. Although the mechanism involved remains unknown, regulation of the arginine-NO pathway by L-glutamine may have pharmacologic and therapeutic implications in such conditions as inflammation and septic shock by inhibiting NO generation from L-arginine in endothelial cells.
 ...
PMID:L-glutamine inhibits nitric oxide synthesis in bovine venular endothelial cells. 910 29

Annual nitrogen (N), phosphorus (P), and potassium (K) flows in agriculture in The Netherlands were identified and quantified in 1990, with special emphasis on pig production. Also, the effects that various management strategies in pig production have on NPK emission in 1990 were compared using a static deterministic simulation model. Ammonia emission from pig production in 1990 (60.9 Gg N) exceeded the defined target for the year 2000 (12.7 Gg N). Measures that affect volatilization of ammonia directly (i.e., introduction of low-emission stables, manure storage facilities, or manure application techniques) reduced ammonia emission most effectively. These measures, however, should be combined with a reduction in application of artificial N fertilizer to avoid an increase in N losses through leaching, run-off, or denitrification. Targets for ammonia emission in the year 2010 require a reduction in the pig population of 24 to 62%, in addition to implications of measures described in this article. National NPK losses in 1990 through leaching, run-off, or denitrification, predicted at 223.5 kg/ha for N, 32.7 kg/ha for P, and 67 kg/ha for K, exceeded government targets for the year 2010 (185 kg N/ha; 8.7 kg P/ha; norm not set for K). Reducing application of artificial NPK fertilizer reduced national NPK losses most effectively. For P, use of phytase and feeding pigs in accordance with their P requirements is required, in addition to limited use of artificial P fertilizer to meet targets for the year 2010. Hence, from an environmental point of view, pig production in The Netherlands is limited primarily by ammonia emission targets for the year 2010.
 ...
PMID:Nutrient flows in agriculture in The Netherlands with special emphasis on pig production. 926 51

A cellular suspension from rat submandibular glands was prepared with collagenase. The intracellular pH (pHi) was estimated with 2',7'-bis-(2-carboxy-ethyl)-5(6)-carboxyfluorescein (BCECF). After exposure to NH4Cl, the pHi transiently increased (diffusion of NH3) and then dropped (influx of NH4+). Isoproterenol increased 2.5-fold the rate of NH4+ influx; bumetanide, an inhibitor of the Na+-K+-2Cl(-)-cotransporter blocked the response to isoproterenol, confirming that the beta-adrenergic agonist stimulated the cotransporter. Forskolin (1 micromol/L) mimicked the response to isoproterenol. VIP (1 nmol/L(-1) micromol/L) also increased the activity of the cotransporter. Cyclic AMP rather than calcium was the mediator of this activation since 1) carbachol which increased the [Ca2+]i fivefold increased the uptake of NH4+ by only 50%; 2) only high concentrations of VIP significantly increased the [Ca2+]i; 3) incubation in the presence of EGTA had no effect on the response to VIP; 4) low concentrations (nmol/L) of the neuropeptide increased the intracellular level of cAMP; and 5) the stimulation of the cotransporter by VIP, forskolin, and isoproterenol was inhibited by H8, an inhibitor of cAMP-dependent protein kinase. It is concluded that the Na+-K+-2Cl(-)-cotransporter of rat submandibular glands is activated by isoproterenol, forskolin, and neuropeptides of the VIP family by a mechanism involving cAMP-dependent processes. The activation of the cotransporter by VIP could partly explain the potentiating effect of VIP on the response to sialagogues like substance P or muscarinic agonists.
 ...
PMID:Activation of the Na+-K+(NH4+)-2Cl(-)- cotransporter from rat submandibular glands in response to VIP. 988 83

The effect of ammonia on the cough response to citric acid and on substance P release from C-fibers involved in this reflex was assessed. For a period from one to four days, piglets were exposed, in an inhalation chamber, to ammonia at a concentration of 15 or 30 ppm. During exposure, cough induction tests were done every two days. Recovery of the cough reflex after ammonia exposure was also determined. In a separate group of piglets exposed for 2 days to 30 ppm ammonia, substance P content was determined in bronchial and tracheal lavage fluids and in the tracheal and bronchial mucosa. Ammonia (30 ppm) was found to inhibit coughing significantly (the cough frequency was reduced by 64%) after a two-day exposure. In animals exposed for 4 days to this ammonia concentration, the recovery ranged from 3 to 7 days (mean: 5 days). The same ammonia concentration also caused the substance P content to increase significantly in bronchoalveolar lavage fluid (to 432% of its initial value) and tracheal lavage fluid (to 149%) and to decrease significantly in the tracheal mucosa (-58%), however the content in bronchial mucosa was not significantly affected (-43%). Exposure to 15 ppm ammonia had no effect on the frequency of citric acid-induced coughing. In conclusion, ammonia inhibits citric acid-induced coughing in pigs at concentrations that can be detected in piggeries. This inhibitory effect may be related to substance-P depletion in C-fiber endings.
 ...
PMID:Inhibiting effect of ammonia on citric acid-induced cough in pigs: a possible involvement of substance P. 1114 Aug 27

Most of the N in surface soils occurs in organic forms, and when mineralized it plays a key role in soil fertility and plant nutrition. Our objective was to study the effect of long-term applications of organic manure on the content and distribution of forms of organic N in bulk soil and soil particle size fractions to characterize the inherent soil nitrogen fertility. Five treatments were as follows: (1) CK (no fertilizer and no manure added), (2) mineral fertilizer only, (3) straw + NPK, (4) green manure + NPK and (5) pig manure + NPK. Soil particle size fractions (0-2, 2-10, 10-50 and 50-100 microm) were isolated without chemical pretreatment by ultrasonic dispersion in water followed by sedimentation. The content of total N and forms of organic N in the bulk soil increased after long-term fertilization, and the effect varied with fertilizer type. The plot treated with only mineral fertilizer gave the highest NH3-N and the lowest amino sugar-N content in all treatments. The highest content of amino sugar-N and amino acid-N was found in the treatment of pig manure + NPK. The content (g kg(-1) fraction) of hydrolysable N within size fractions was in the order 0-2 > 2-10 > 50-100 > 10-50 microm, but the contribution of different size fraction to hydrolysable N decreased in the sequence 10-50 > 0-2 > 2-10 > 50-100 microm. Most of the applied mineral fertilizer N that remained in soils was distributed in the particle size fraction < 2 microm while most of the remaining N from manure applied with NPK was transferred into amino sugar-N in each size fraction, and amino acid-N in the size fractions > 2 microm during the process of humification.
 ...
PMID:Content and distribution of forms of organic N in soil and particle size fractions after long-term fertilization. 1268 85


1 2 3 4 Next >>