John Libbey Eurotext

Magnesium Research


Neutral endopeptidase inhibition enhances substance P mediated inflammation due to hypomagnesemia Volume 22, numéro 3, september 2009

Departments of Biochemistry & Molecular Biology, Medicine, The George Washington University Medical Center, Washington, the Division of Cardiology, Children’s National Medical Center, Washington, Children’s Hospital, Harvard Medical School, Boston, USA
  • Mots-clés : hypomagnesemia, NEP inhibition, substance P, neutrophil activation, oxidative/nitrosative stress, NEP knockout mice
  • DOI : 10.1684/mrh.2009.0181
  • Page(s) : 167-73
  • Année de parution : 2009

During dietary deficiency of magnesium neurogenic inflammation is mediated, primarily, by elevated levels of substance P (SP). The enzyme most specific for degrading this neuropeptide is neutral endopeptidase (NEP). In recent studies we found that pharmacological inhibition of NEP by phosphoramidon resulted in elevated plasma levels of SP and greater oxidative stress. We also observed that hypomagnesemia reduced cardiac and intestinal expression of NEP. In these magnesium-deficient rats increased intestinal permeability and impaired cardiac contractility occurred. In our colony of genetically-engineered NEP knockout mice that have reduced ability to degrade SP, we found increased oxidative stress that was prevented by SP (neurokinin-1) receptor blockade. Thus, we submit that inhibition of NEP by pharmacological, genetic and dietary approaches (magnesium restriction), causes greater neurogenic inflammation that may result in increased intestinal and cardiac dysfunction.