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Article

  • The EMBO Journal (2006) 25, 3024 - 3032
  • doi:10.1038/sj.emboj.7601207

Published online: 29 June 2006

Calcium-dependent release of NO from intracellular S-nitrosothiols

Michael Chvanov, Oleg V Gerasimenko, Ole H Petersen and Alexei V Tepikin

  1. The Physiological Laboratory, The University of Liverpool, Liverpool, UK

Correspondence to:

Alexei V Tepikin, Department of Physiology, The University of Liverpool, Crown Street, PO Box 147, Liverpool L69 3BX, UK. Tel.: +44 151 794 5351; Fax: +44 151 794 5327; E-mail: a.tepikin@liv.ac.uk

Michael Chvanov, Department of Physiology, The University of Liverpool, Crown Street, PO Box 147, Liverpool L69 3BX, UK. Tel.: +44 151 794 5351; Fax: +44 151 794 5327; E-mail: chvanov@liv.ac.uk

Received 10 January 2006; Accepted 30 May 2006

The paper describes a novel cellular mechanism for rapid calcium-dependent nitric oxide (NO) release. This release occurs due to NO liberation from S-nitrosothiols. We have analysed the changes of NO concentration in acutely isolated pancreatic acinar cells. Supramaximal acetylcholine (ACh) stimulation induced a Ca2+-dependent increase in the fluorescence in the majority of cells loaded with the NO probe DAF-FM via a patch pipette. The ACh-induced NO signals were insensitive to inhibitors of calmodulin and protein kinase C but were inhibited by calpain antagonists. The initial part of the NO signals induced by 10 muM ACh showed little sensitivity to inhibition of NO synthase (NOS); however, cell pretreatment with NO donors (increasing cellular S-nitrosothiol contents) substantially enhanced the initial component of NO responses. Pancreatic acinar cells were able to generate fast calcium-dependent NO responses when stimulated with physiological or supramaximal doses of secretagogues. Importantly, the source of this NO is the already available S-nitrosothiol store rather than de novo synthesis by NOS. A similar mechanism of NO release was found in dorsal root ganglia neurons.

  • Keywords:

    • calcium,
    • glutathione,
    • nitric oxide,
    • NOS,
    • S-nitrosothiols