PMID: 8971937Jan 1, 1996Paper

Substance P and neurokinin A metabolism by cultured human skeletal muscle myocytes and fibroblasts

Peptides
J S RussellP E Ward

Abstract

A recent study determined that cultured human skeletal muscle adult myoblasts, myotubes, and fibroblasts degraded angiotensins and kinins via neutral endopeptidase-24.11 (NEP-24.11: EC 3.4.24.11) and aminopeptidase N (APN: EC 3.4.11.2). Due to the possible importance of other peptides to skeletal muscle blood flow and function, the present study looked specifically at the metabolism of the neurokinins substance P (SP) and neurokinin A (NKA) by skeletal muscle peptidases. The results show that SP is degraded not only by NEP-24.11, but also sequentially by dipeptidyl(amino)peptidase IV (DAP IV: EC 3.4.14.5)/APN. NKA is unaffected by DAP IV but is metabolized by NEP-24.11 and APN. NEP-24.11 was inhibited by phosphoramidon (IC50 = 80 nM), thiorphan and ZINCOV, DAP IV by diprotin A (IC50 = 8 microM), and APN by amastatin (IC50 = 50 nM) and bestatin (IC50 = 100 microM). Skeletal muscle myocyte and fibroblast metabolism of SP and NKA may regulate local skeletal muscle vascular and extravascular functions including SP- and NKA-mediated nerve-induced vasodilation. Inhibition of both NEP-24.11 and DAP IV/APN may increase skeletal muscle blood flow and decrease peripheral vascular resistance via potentiation of local neurokinin levels.

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Citations

Dec 12, 2001·Toxicon : Official Journal of the International Society on Toxinology·Steven D Aird
Aug 10, 2001·Regulatory Peptides·I PrietoM Ramírez
Dec 23, 2003·The International Journal of Biochemistry & Cell Biology·Petr BusekAleksi Sedo
Nov 7, 2006·Immunology and Allergy Clinics of North America·James Brian ByrdNancy J Brown
Feb 18, 2009·Clinical and Experimental Immunology·S Grigoriadou, H J Longhurst
Oct 11, 2011·The Journal of Dermatology·Keiko TanakaShinji Shimada
Apr 22, 2014·Expert Opinion on Drug Metabolism & Toxicology·Theodosios D FilippatosMoses S Elisaf
Nov 28, 2012·Allergology International : Official Journal of the Japanese Society of Allergology·Naoko Inomata
Jul 9, 2009·International Review of Cell and Molecular Biology·J Michael Sorrell, Arnold I Caplan
May 23, 2002·The Journal of Pharmacology and Experimental Therapeutics·Timothy D WestfallJ Paul Hieble
Nov 2, 2020·Experimental Dermatology·Payal M PatelKyle T Amber
Mar 3, 2020·Thérapie·Marion LepelleyLaurence Bouillet
Aug 1, 2021·Journal of Investigative Medicine High Impact Case Reports·Chidinma EjikemeMicheal Brescia
Dec 8, 2021·Clinical and Molecular Allergy : CMA·Nicoletta CassanoCaterina Foti

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