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ToxSci Advance Access published online on July 13, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl061
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 10, 2006
Accepted July 10, 2006

Respiratory Toxicology

Adenosine Sensory Transduction Pathways Contribute to Activation of the Sensory Irritation Response to Inspired Irritant Vapors

Ryan P. Vaughan 1, Michael T. Szewczyk Jr. 1, Michael J. Lanosa 1, Christopher R. DeSesa 1, Gerald Gianutsos 1, and John B. Morris 1 *

1 Toxicology Program, Dept. of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT

* To whom correspondence should be addressed.
John B. Morris, E-mail: john.morris{at}uconn.edu


  Abstract

The molecular mechanisms through which sensory irritants stimulate nasal trigeminal nerves are poorly understood. The current study was aimed at evaluating the potential contribution of purinergic sensory transduction pathways in this process. Aerosols of 4-36 mM ATP and adenosine both acted as sensory irritants. Large dose capsaicin pretreatment to induce degeneration of TRPV1-expressing C fibers greatly reduced, but did not abolish, the sensory irritation response to ATP aerosol and was without effect on the response to adenosine aerosol, indicating that ATP acts largely on capsaicin-sensitive (primarily C fibers) and adenosine acts on capsaicin-insensitive (primarily A{delta} fibers) nerves. The response to adenosine was diminished by pretreatment with the broad-based adenosine receptor antagonist theophylline (20 mg/kg) and A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg), providing evidence that adenosine stimulates capsaicin-insensitive nerves via the A1 receptor. The sensory irritation response to 275 ppm styrene and 110 ppm acetic acid vapors were significantly reduced by theophylline pretreatment suggesting a role for adenosine signaling pathways in activation of the sensory irritant response by these vapors. If sensory nerves are activated by mediators that are released from injured airway mucosal cells then nasal sensory nerve activation may be a reflection of irritant-induced alterations in airway cell integrity.

Keywords: sensory irritation; adenosine; acetic acid; styrene.
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