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Am J Physiol Lung Cell Mol Physiol (April 12, 2002). doi:10.1152/ajplung.00376.2001
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Articles in PresS, published online ahead of print April 12, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00376.2001
Submitted on September 20, 2001
Accepted on March 21, 2002

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

Joris Kloek1, Ingrid Van Ark1, Nanne Bloksma2, Fred De Clerck3, Frans P. Nijkamp1, and Gert Folkerts1*

1 Pharmacology & Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands
2 Pharmacology & Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Faculty of Biology, Utrecht, The Netherlands
3 Pharmacology & Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Cardiovascular and Inflammation Pharmacology, Janssen Research Foundation, Beerse, Belgium

* To whom correspondence should be addressed. E-mail: G.Folkerts{at}pharm.uu.nl.

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), and the high (millimolar) concentrations of GSH in trachea epithelium. GSH and other thiols (1.0 - 10 mM) dose-dependently decreased the tension in isolated guinea pig tracheas. Relaxations by GSH were paralleled with 7-fold increased nitrite levels (P<0.05) in the tracheal effluent, suggesting an interaction between GSH and NO. However, preincubation with an 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 anti-oxidative action of GSH itself, rather than an action of NO or GSNO.






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