Biological activity of designed photolabile metal nitrosyls: light-dependent activation of soluble guanylate cyclase and vasorelaxant properties in rat aorta

Research output: Contribution to journalArticlepeer-review

Authors

  • Apurba K Patra
  • Thomas W Miller
  • Aura A Eroy-Reveles
  • Adrian J Hobbs
  • Jon M Fukuto
  • Pradip K Mascharak

Colleges, School and Institutes

Abstract

The biological and pharmacological utility of nitric oxide (NO) has led to the development of many classes of NO-donor compounds as both research tools and therapeutic agents. Many donors currently in use rely on thermal decomposition or bioactivation for the release of NO. We have developed several photolabile metal-nitrosyl donors that release NO when exposed to either visible or UV light. Herein, we show that these donors are capable of activating the primary "NO receptor", soluble guanylate cyclase (sGC), in a light-dependent fashion leading to increases in cGMP. Moreover, we demonstrate that these donors are capable of eliciting light-dependent increases of cGMP in smooth muscle cells and vasorelaxation of rat aortic smooth muscle tissue, all effects that are attributed to activation of sGC. The potential utility of these compounds as drugs and/or research tools is discussed.

Details

Original languageEnglish
Pages (from-to)7325-30
Number of pages6
JournalJournal of Medicinal Chemistry
Volume49
Issue number25
Publication statusPublished - 14 Dec 2006

Keywords

  • Animals, Aorta, Cells, Cultured, Cyclic GMP, Enzyme Activation, Guanylate Cyclase, In Vitro Techniques, Iron, Light, Manganese, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Nitric Oxide Donors, Organometallic Compounds, Rats, Receptors, Cytoplasmic and Nuclear, Ruthenium, Structure-Activity Relationship, Vasodilation, Vasodilator Agents