Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether exogenously administered neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) inhibits the substance P-induced increase in vascular permeability in the skin, we examined the effects of recombinant human NEP on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. Injection of substance P (2.5 X 10(-8) M) induced significant plasma extravasation in the skin (53 +/- 4 mm2 of Evans blue extravasation; mean +/- 1 SEM). In vitro incubation of substance P with recombinant human NEP prior to injection prevented the substance P-induced plasma extravasation in the skin in a dose-dependent fashion. Intradermal preinjection of recombinant human NEP partially inhibited plasma extravasation induced by subsequent injection of substance P (52 +/- 9% of the control without NEP). The H1 and H2 histamine antagonists pyrilamine and cimetidine, and a muscarinic antagonist, atropine, had no effects on substance P-induced responses. Two products of substance P degradation by NEP containing the carboxy-terminal portion, substance P7-11 and substance P8-11, were also without effect. These findings suggest that recombinant human NEP can attenuate substance P-induced increases in vascular permeability in guinea pig skin and, therefore, may be useful in treating dermatologic disorders in which abnormal responses to substance P or other neuropeptides cleaved by NEP may occur.
 ...
PMID:Recombinant neutral endopeptidase attenuates substance P-induced plasma extravasation in the guinea pig skin. 169 12

Nine mongrel dogs were anesthetized, paralysed, ventilated, and placed in an iron lung. Each animal was transiently connected to a spirometer and the respiratory system compliance measured by applying negative or positive extrathoracic pressures (from -20 cm H2O to +20 cm H2O in 5 cm H2O steps). A sub-lobar bronchus was wedged with a 5.5 mm bronchoscope, and a 5f Swan-Ganz catheter was inserted into the lumen of the bronchoscope; one port served to introduce a 200 ml.min-1 flow of 5% CO2 in air, the other to measure the pressure in the wedged segment. Rcoll was measured with extrathoracic pressures in the iron lung ranging from 0 to -20 cm H2O (NEP) and 0 to +20 cm H2O (PEP) in 5 cm H2O steps, and under expiratory positive airway pressure (EPAP) of 5, 10, 15, and 20 cm H2O. The maximal changes in FRC were an increase of 1009 +/- 49 ml (mean +/- SEM) with NEP and a decrease of 397 +/- 33 ml with PEP. Increasing FRC decreased Rcoll while decreasing FRC markedly increased it. EPAP induced similar decreases in Rcoll as NEP of equal pressure. This effect of EPAP was inhibited by simultaneously applying PEP of equal pressure. We conclude that resistance to collateral flow is highly dependent on lung volume, and that positive airway pressure decreases Rcoll by its effects on lung volume.
 ...
PMID:Effects of lung volume and positive airway pressure on collateral resistance. 236 48

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.
 ...
PMID:Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line. 256 5

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/- 1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7 micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive findings in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.
 ...
PMID:Increased serum neutral endopeptidase activity in acute renal allograft rejection. 873 78

The purpose of this study was to determine whether neutral endopeptidase (NEP; EC3.4.24.11) is decreased in the uvula epithelium of patients with obstructive sleep apnea (OSA). Tissues were obtained by uvulopharyngopalatoplasty in seven patients with moderate OSA and by autopsy in five individuals not known to have OSA. Using antisera to human NEP and immunoperoxidase staining, we found that NEP was localized in uvula epithelial cells of both patients with OSA and controls. However, there was a significant decrease in the number of epithelial cells staining for NEP in patients with OSA relative to controls (67 +/- 10 cells versus 261 +/- 33 cells, in 5 randomly selected high-power microscopic fields, respectively; mean +/- SEM; p < .05). The intensity of staining for NEP was similar in both groups. We conclude that immunoreactive NEP is significantly decreased in the uvula epithelium of patients with OSA.
 ...
PMID:Decrease in immunoreactive neutral endopeptidase in uvula epithelium of patients with obstructive sleep apnea. 919 6