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)

It has recently been demonstrated that luminal exposure of airway segments in vitro to HOCl produces airway muscle hyperresponsiveness to substance P and a decrease in neutral endopeptidase (NEP) activity of tissue segment homogenates, suggesting that HOCl may decrease airway epithelial cell NEP activity. To confirm that this effect occurs in humans and to investigate possible subcellular mechanisms for it, we assessed HOCl exposure of the human airway epithelial cell line Calu-1. These cells, grown to confluency in Dulbecco's modified Eagle medium with 10% fetal bovine serum and penicillin-streptomycin, were exposed in situ for 5 min to 100 microM HOCl in a phosphate-buffered saline solution (PBS; pH 7.0 at 37 degrees C) or to PBS alone. Thereafter, cells were rinsed and assayed for NEP activity employing reverse-phase high-pressure liquid chromatography. This activity was characterized by the generation of phosphoramidon-inhibitable product (ANA) cleaved from the synthetic substrate succinyl-(ala)3-p-nitroaniline during a 30 min incubation at 37 degrees C. Cell viability was assessed by changes in LDH release, trypan blue exclusion, and cell volume. In some experiments, crude plasma membrane and soluble components of exposed cells were isolated and differential NEP activity was assayed. We found that a 5 min exposure to HOCl decreased whole cell NEP activity from 74.1 +/- 4.4 (mean +/- SE) to 54.3 +/- 6.0 pmoles of ANA/min/10(6) cells (p less than 0.05), while no parameter of cell viability was affected. NEP activity in the crude membrane fraction decreased 36.3 +/- 3.1% after exposure (p less than 0.01), whereas NEP activity in the soluble fraction increased 4.0 +/- 0.6%. Isolated membrane NEP exposed by itself was not affected. Subsequent experiments with reducing agents demonstrated that NEP activity of cell cultures pretreated with 100 mM of either beta-mercaptoethanol or dithiothrietol before HOCl exposure was not significantly different from control values. We conclude that whole cell HOCl exposure decreases Calu-1 plasma membrane NEP. This loss appears to occur by internalization of cell membrane NEP.
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PMID:HOCl exposure of a human airway epithelial cell line decreases its plasma membrane neutral endopeptidase. 166 4

Release of immunoreactive somatostatin (I-SRIF) and immunoreactive substance P (I-SP) was studied from slices prepared from upper dorsal horn (UDH) and lower dorsal plus ventral horn (LDH-VH) of rat spinal cord. Superfusion with capsaicin (10 microM) led to release of I-SRIF and I-SP from UDH slices but not from LDH-VH slices. The capsaicin-evoked release of I-SP was 6 fold higher than that of I-SRIF. A pulse of 60 mM K+ applied after the capsaicin pulse caused release of I-SRIF and I-SP from UDH as well as LDH-VH slices. Pretreatment of rats with capsaicin (125 mg/kg, s.c.) led to a nearly 40% depletion of I-SP in slices from UDH only. Capsaicin-evoked release from these slices was reduced by 81% for I-SRIF and by 79% for I-SP. Release evoked by K+ remained unchanged. These results indicate that capsaicin causes release of both I-SRIF and-I-SP and that this release is most likely restricted to primary sensory neurons. The marked reduction of the release of I-SP after systemic capsaicin pretreatment may well represent one of the, or even the reason for the insensitivity of capsaicin pretreated rats towards chemogenic pain.
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PMID:Effect of capsaicin pretreatment on capsaicin-evoked release of immunoreactive somatostatin and substance P from primary sensory neurons. 616 21

Severe dietary Mg restriction (Mg(9), 9% of recommended daily allowance [RDA], plasma Mg = 0.25 mM) induces a pro-inflammatory neurogenic response in rats (substance P [SP]), and the associated increases in oxidative stress in vivo and cardiac susceptibility to ischemia/reperfusion (I/R) injury were previously shown to be attenuated by SP receptor blockade and antioxidant treatment. The present study assessed if less severe dietary Mg restriction modulates the extent of both the neurogenic/oxidative responses in vivo and I/R injury in vitro. Male Sprague-Dawley rats maintained on Mg(40) (40% RDA, plasma Mg = 0.6 mM) or Mg(100) (100% RDA, plasma Mg = 0.8 mM) diets were assessed for plasma SP levels (CHEM-ELISA) during the first 3 weeks and were compared with the Mg(9) group; red blood cell (RBC) glutathione and plasma malondialdehyde levels were compared at 3 weeks in Mg(9), Mg(20) (plasma Mg = 0.4 mM), Mg(40), and Mg(100) rats; and 40-min global ischemia/30-min reperfusion hearts from 7-week-old Mg(20), Mg(40), and Mg(100) rats were compared with respect to functional recovery (cardiac work, and diastolic, systolic, and developed pressures), tissue LDH release, and free radical production (ESR spectroscopy and alpha-phenyl-N-tert butylnitrone [PBN; 3 mM] spin trapping). The Mg(40) diet induced smaller elevations in plasma SP (50% lower) compared with Mg(9), but with a nearly identical time course. RBC glutathione and plasma malondialdehyde levels revealed a direct relationship between the severity of oxidative stress and hypomagnesemia. The dominant lipid free radical species detected in all I/R groups was the alkoxyl radical (PBN/alkoxyl: alpha(H) = 1.93 G, alpha(N) = 13.63 G); however, Mg(40) and Mg(20) hearts exhibited 2.7- and 3.9-fold higher alkoxyl levels, 40% and 65% greater LDH release, and lower functional recovery (Mg(20) < Mg(40)) compared with Mg(100). Our data suggest that varying dietary Mg intake directly influences the magnitude of the neurogenic/oxidative responses in vivo and the resultant myocardial tolerance to I/R stress.
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PMID:Dietary magnesium intake influences circulating pro-inflammatory neuropeptide levels and loss of myocardial tolerance to postischemic stress. 1277 97