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Am J Physiol Lung Cell Mol Physiol 283: L403-L408, 2002. First published April 12, 2002; doi:10.1152/ajplung.00376.2001
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Vol. 283, Issue 2, L403-L408, August 2002

Glutathione and other low-molecular-weight thiols relax guinea pig trachea ex vivo: interactions with nitric oxide?

Joris Kloek1, Ingrid van Ark1, Nanne Bloksma1,2, Fred De Clerck1,3, Frans P. Nijkamp1, and Gert Folkerts1

Department of Pharmacology and Pathophysiology, 1 Faculty of Pharmaceutical Sciences, and 2 Faculty of Biology, Utrecht University, 3508 TB Utrecht, The Netherlands; and 3 Department of Cardiovascular and Inflammation Pharmacology, Janssen Research Foundation, B-2340 Beerse, Belgium

The aim of this study was to determine the effects of glutathione (GSH) on trachea smooth muscle tension in view of previously reported interactions between GSH and nitric oxide (NO) (Gaston B. Biochim Biophys Acta 1411: 323-333, 1999; Kelm M. Biochim Biophys Acta 1411: 273-289, 1999; and Kharitonov VG, Sundquist AR, and Sharma VS. J Biol Chem 270: 28158-28164, 1995) and the high (millimolar) concentrations of GSH in trachea epithelium (Rahman I, Li XY, Donaldson K, Harrison DJ, and MacNee W. Am J Physiol Lung Cell Mol Physiol 269: L285-L292, 1995). GSH and other thiols (1.0-10 mM) dose dependently decreased the tension in isolated guinea pig tracheas. Relaxations by GSH were paralleled with sevenfold increased nitrite levels (P < 0.05) in the tracheal effluent, suggesting an interaction between GSH and NO. However, preincubation with a NO scavenger did not reduce the relaxations by GSH or its NO adduct, S-nitrosoglutathione (GSNO). Inhibition of guanylyl cyclase inhibited the relaxations induced by GSNO, but not by GSH. Blocking potassium channels, however, completely abolished the relaxing effects of GSH (P < 0.05). Preincubation of tracheas with GSH significantly (P < 0.05) suppressed hyperreactivity to histamine as caused by removal of tracheal epithelium. These data indicate that GSH plays a role in maintaining tracheal tone. The mechanism is probably an antioxidative action of GSH itself rather than an action of NO or GSNO.

nitrosothiols; epithelium; potassium channels; guanylyl cyclase




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