TY - JOUR
TI - Involvement of 3′,5′-cyclic inosine monophosphate in cystathionine γ-lyase-dependent regulation of the vascular tone
AU - Mitidieri, E.
AU - Vellecco, V.
AU - Brancaleone, V.
AU - Vanacore, D.
AU - Manzo, O.L.
AU - Martin, E.
AU - Sharina, I.
AU - Krutsenko, Y.
AU - Monti, M.C.
AU - Morretta, E.
AU - Papapetropoulos, A.
AU - Caliendo, G.
AU - Frecentese, F.
AU - Cirino, G.
AU - Sorrentino, R.
AU - d'Emmanuele di Villa Bianca, R.
AU - Bucci, M.
JO - British Journal of Pharmacology
PY - 2021
VL - 178
TODO - 18
SP - 3765-3782
PB - John Wiley and Sons Inc
SN - 0007-1188, 1476-5381
TODO - 10.1111/bph.15516
TODO - cyclic IMP;  cystathionine gamma lyase;  guanylate cyclase;  hydrogen sulfide;  nitric oxide synthase;  phosphodiesterase IV;  phosphodiesterase V;  cyclic GMP;  cystathionine gamma lyase;  hydrogen sulfide;  inosine phosphate;  nitric oxide, adult;  animal experiment;  animal model;  Article;  C57BL 6 mouse;  carotid artery;  controlled study;  electrospray mass spectrometry;  Fourier transform mass spectrometry;  high performance liquid chromatography;  immunoblotting;  in vitro study;  liquid chromatography-mass spectrometry;  major clinical study;  male;  mouse;  nonhuman;  proton nuclear magnetic resonance;  reversed phase high performance liquid chromatography;  thoracic aorta;  ultra performance liquid chromatography;  vasodilatation;  Western blotting;  wild type;  animal;  liquid chromatography;  tandem mass spectrometry, Animals;  Chromatography, Liquid;  Cyclic GMP;  Cystathionine gamma-Lyase;  Hydrogen Sulfide;  Inosine Monophosphate;  Mice;  Nitric Oxide;  Tandem Mass Spectrometry
TODO - Background and Purpose: l-cysteine or hydrogen sulfide (H2S) donors induce a biphasic effect on precontracted isolated vessels. The contractile effect occurs within a concentration range of 10 nM to 3 μM followed by vasodilatation at 30–100 μM. Here, we have investigated the signalling involved in the H2S-induced contraction. Experimental Approach: Vascular response to NaHS or l-cysteine is evaluated on isolated precontracted with phenylephrine vessel rings harvested from wild type, cystathionine γ-lyase (CSE−/−), soluble guanylyl cyclase (sGCα1−/−) and endothelial nitric oxide synthase (eNOS−/−) knock-out mice. The cAMP, cGMP and inosine 3′,5′-cyclic monophosphate (cIMP) levels are simultaneously quantified using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) analysis. The involvement of sGC, phosphodiesterase (PDE) 4A and PDE5 are also evaluated. Key Results: CSE-derived H2S-induced contraction requires an intact eNOS/NO/sGC pathway and involves cIMP as a second messenger. H2S contractile effect involves a transient increase of cGMP and cAMP metabolism caused by PDE5 and PDE4A, thus unmasking cIMP contracting action. The stable cell-permeable analogue of cIMP elicits concentration-dependent contraction on a stable background tone induced by phenylephrine. The lack of cIMP, coupled to the hypocontractility displayed by vessels harvested from CSE−/− mice, confirms that H2S-induced contraction involves cIMP. Conclusion and Implications: The endothelium dynamically regulates vessel homeostasis by modulating contractile tone. This also involves CSE-derived H2S that is mediated by cIMP. © 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
ER -