Nitrogen monoxide transport mechanisms.
The present article focuses on the possible existence of transport forms of nitrogen monoxide (NO) in biological tissues. Stimulated by the present controversy on the identity of L-arginine-derived endothelium-derived relaxing factor (EDRF) experiments were designed to clarify whether or not EDRF is a nitrosyl-iron complex. Synthetic dinitrosyl-iron-di-L-cysteine--(NO)2Fe(L-cysteine)2, a low molecular mass dinitrosyl-iron-dihiolate complex (DNIC)--exhibits similar pharmacological properties as EDRF. It is a potent (EC50 10 nmol/l) endothelium-independent, labile (< 2 min), superoxide radical-sensitive vasodilator and a direct activator of soluble guanylyl cyclase. In stimulated endothelial cells a paramagnetic DNIC associated with intracellular proteins was detected by electron spin resonance (ESR) spectroscopy. In the presence of N-acetyl-L-cysteine a low molecular mass DNIC released from endothelial cells was specifically trapped and detected in the extracellular medium as a paramagnetic albumin-DNIC. Due to release of DNIC the content of endothelial non-heme iron decreased after prolonged (1 h) agonist-induced stimulation in iron-free medium. Therefore, it is conceivable that endothelial NO forms high molecular (protein-bound) and low molecular DNIC. The protein-bound DNIC may serve as a reservoir for low molecular DNIC. The low molecular DNIC permeates the cell membrane and may thus act as an EDRF. The biological significance of DNIC may reside less in stabilization of free NO than in modulation of its reactivity. Thus, it is conceivable that DNIC reacts more selectively with proteins essential for NO-mediated signal transduction. By this mechanism signal transduction by NO will become more efficient and directed to certain pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
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Zentrum der Physiologie, Klinikum der Johann Wolfgang von Goethe-Universität, Frankfurt/Main, Fed. Rep. of Germany.
D000818:Animals; D001693:Biological Transport, Active; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D007501:Iron