Neutral endopeptidase-like enzyme controls the contractile activity of substance P in guinea pig lung.

Stimler-Gerard, Norma P.

doi:10.1172/jci113023

Cited by 103 publications

(41 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NEP is a zinc-containing metalloendopeptidase involved in the degradation of several regulatory peptides and plays an important role in turning off peptide signaling events on the cell surface. 23,39,40 It is expressed on the surface of polymorphonuclear leukocytes and in several organs, including the kidney, in which it is localized, with a high density, on the brush border of proximal tubular CLINICAL RESEARCH www.jasn.org cells and on the cell surface of glomerular podocytes. 41,42 Debiec et al 42,43 showed that NEP may represent the target antigen in a rare subset of patients with alloimmune antenatal membranous nephropathy.…”

Section: Discussionmentioning

confidence: 99%

The Anti-Fibrotic Effect of Mycophenolic Acid–Induced Neutral Endopeptidase

Dell'Oglio

Zaza

Rossini

et al. 2010

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Mycophenolic acid (MPA) appears to have anti-fibrotic effects, but the molecular mechanisms underlying this are unknown. We prospectively studied 35 stable kidney transplant recipients maintained on cyclosporine and azathioprine. We converted 20 patients from azathioprine to enteric-coated mycophenolate sodium (EC-MPS) and continued the remaining 15 patients on azathioprine. Exploratory mRNA expression profiling, performed on five randomly selected EC-MPS patients, revealed significant upregulation of neutral endopeptidase (NEP), which is an enzyme that degrades angiotensin II. We confirmed these microarray data by measuring levels of NEP expression in all subjects; in addition, we found that NEP gene expression correlated inversely with proteinuria. In an additional 33 patients, glomerular and tubular NEP protein levels from renal graft biopsies were significantly higher among the 13 patients receiving cyclosporine ϩ EC-MPS than among the 12 patients receiving cyclosporine ϩ azathioprine or 8 patients receiving cyclosporine alone. Glomerular NEP expression inversely correlated with glomerulosclerosis and proteinuria, and tubular NEP expression inversely correlated with interstitial fibrosis. Incubation of human proximal tubular cells with MPA increased NEP gene expression in a doseand time-dependent manner. Moreover, MPA reduced angiotensin II-induced expression of the profibrotic factor plasminogen activator inhibitor-1, and a specific NEP inhibitor completely reversed this effect. Taken together, our data suggest that MPA directly induces expression of neutral endopeptidase, which may reduce proteinuria and slow the progression of renal damage in kidney transplant recipients. 21: 215721: -216821: , 201021: . doi: 10.1681 Over the last decade, the continuous progress in the development of immunosuppressive agents has enhanced both the efficacy and safety of antirejection regimens after renal transplantation, leading to a dramatic reduction in the incidence of acute rejection. 1 This significant improvement in short-term graft outcome was not followed by a similar advance in preventing graft loss caused by chronic graft injury. 2,3 The addition of mycophenolic acid (MPA) into contemporary immunosuppressive regimens represented an important step forward in the development of new therapeutic protocols in kidney transplantation. J Am Soc NephrolMPA exerts its immunosuppressive effect by inhibiting the inosine 5Ј monophosphate dehydro-

show abstract

Section: Discussionmentioning

confidence: 99%

The Anti-Fibrotic Effect of Mycophenolic Acid–Induced Neutral Endopeptidase

Dell'Oglio

Zaza

Rossini

et al. 2010

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…These studies revealed that tachykinin and capsaicin receptor pharmacology is very similar in human and guinea pig airways, and in both species tachykinins are metabolized in the lung by neutral endopeptidase [253,[288][289][290][291]. Despite many important and fundamental discoveries relating to afferent nerve excitability, the axon reflex and tachykinin and capsaicin receptor pharmacology, it now seems likely that the axon reflex as it manifests in the lungs of guinea pigs and rats is not present in the human lung.…”

Section: Axon Reflexmentioning

confidence: 99%

Using guinea pigs in studies relevant to asthma and COPD

Canning

Chou

2008

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

The guinea pig has been the most commonly used small animal species in preclinical studies related to asthma and COPD. The primary advantages of the guinea pig are the similar potencies and efficacies of agonists and antagonists in human and guinea pig airways and the many similarities in physiological processes, especially airway autonomic control and the response to allergen. The primary disadvantages to using guinea pigs are the lack of transgenic methods, limited numbers of guinea pig strains for comparative studies and a prominent axon reflex that is unlikely to be present in human airways. These attributes and various models developed in guinea pigs are discussed.

show abstract

“…This zinc metalloprotease cleaves a variety of bioactive peptides including tachykinins such as bradykinin and substance P (2,(4)(5)(6). CD1O/NEP downregulates neurogenic inflammation ofthe lung by modulating locally effective concentrations of tachykinins (7)(8)(9)(10). The enzyme has been found to hydrolyze bombesin-like peptides (BLPs) within the conserved seven amino acid terminus required for biological activity (reviewed in 11,12,13 ).…”

Section: Introductionmentioning

confidence: 99%

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

King¹,

Hua²,

Torday³

et al. 1993

J. Clin. Invest.

View full text Add to dashboard Cite

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CDI0/NEP regulates peptide-mediated lung development, we administered a specific CD1O/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on el8 for: (a) growth using [3HIthymidine incorporation into nuclear DNA; and (b) maturation using: 13H1-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10 / NEP stimulated [3HIthymidine incorporation into DNA (70% above baseline, P < 0.005), 13Hlcholine incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, IDPhe'2, Leu14jbombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. (J. Clin. Invest. 1993. 91:1969-1973.) Key words: metalloendopeptidase * autocrine growth factors * fetal lung development * cell surface enzyme * common acute lymphoblastic leukemia antigen

show abstract

Neutral endopeptidase-like enzyme controls the contractile activity of substance P in guinea pig lung.

Cited by 103 publications

References 37 publications

The Anti-Fibrotic Effect of Mycophenolic Acid–Induced Neutral Endopeptidase

The Anti-Fibrotic Effect of Mycophenolic Acid–Induced Neutral Endopeptidase

Using guinea pigs in studies relevant to asthma and COPD

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

Contact Info

Product

Resources

About