%0 Journal Article
%T Pharmacological hypothesis: Nitric oxideİ\induced inhibition of ADAMİ\17 activity as well as vesicle release can in turn prevent the production of soluble endothelinİ\converting enzyme
%A Helena C. Parkington
%A Ian Smith
%A Niwanthi W. Rajapakse
%A Sanjaya Kuruppu
%J Archive of "Pharmacology Research & Perspectives".
%D 2017
%R 10.1002/prp2.335
%X Endothelinİ\1 (ETİ\1) and nitric oxide (NO) are two highly potent vasoactive molecules with opposing effects on the vasculature. Endothelinİ\converting enzyme (ECE) and nitric oxide synthase (NOS) catalyse the production of ETİ\1 and NO, respectively. It is well established that these molecules play a crucial role in the initiation and progression of cardiovascular diseases and have therefore become targets of therapy. Many studies have examined the mechanism(s) by which NO regulates ETİ\1 production. Expression and localization of ECEİ\1 is a key factor that determines the rate of ETİ\1 production. ECEİ\1 can either be membrane bound or be released from the cell surface to produce a soluble form. NO has been shown to reduce the expression of both membraneİ\bound and soluble ECEİ\1. Several studies have examined the mechanism(s) behind NOİ\mediated inhibition of ECE expression on the cell membrane. However, the precise mechanism(s) behind NOİ\mediated inhibition of soluble ECE production are unknown. We hypothesize that both exogenous and endogenous NO, inhibits the production of soluble ECEİ\1 by preventing its release via extracellular vesicles (e.g., exosomes), and/or by inhibiting the activity of A Disintegrin and Metalloproteaseİ\17 (ADAM17). If this hypothesis is proven correct in future studies, these pathways represent targets for the therapeutic manipulation of soluble ECEİ\1 production
%K Endothelinİ\converting enzyme
%K nitric oxide
%K protein kinase C
%K trafficking
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625149/