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This Article Full Text Full Text (PDF) All Versions of this Article: 106/4/1142    most recent 91229.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lin, Y. S. Articles by Kou, Y. R. Search for Related Content PubMed PubMed Citation Articles by Lin, Y. S. Articles by Kou, Y. R.

Sensitization of capsaicin-sensitive lung vagal afferents by anandamide in rats: role of transient receptor potential vanilloid 1 receptors

¹Department of Physiology, School of Medicine and ³School of Respiratory Therapy, Taipei Medical University; ²Department of Physiology, School of Medicine, National Yang-Ming University; and ⁴Department of Otolaryngology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan

Submitted 15 September 2008 ; accepted in final form 6 January 2009

Anandamide (AEA), an arachidonic acid derivative produced during inflammatory conditions, is an endogenous agonist of both transient receptor potential vanilloid 1 (TRPV1) receptors and cannabinoid CB1 receptors. Sensitization of capsaicin-sensitive lung vagal afferent (CSLVA) fibers by chemical mediators is important in the pathogenesis of hyperreactive airway diseases. We investigated the effect of the intravenous infusion of AEA (2 mg·kg^–1·ml^–1, 0.5 ml/min for 2 min) on the sensitivity of CSLVA fibers to chemical and mechanical stimulation in anesthetized rats. In artificially ventilated rats, AEA infusion only mildly elevated the baseline activity of CSLVA fibers. However, CSLVA fiber responses to right atrial injection of capsaicin, AEA, or adenosine and to lung inflation (tracheal pressure = 30 cmH₂O) were all markedly potentiated during AEA infusion, which reverted 20 min after termination of the infusion. The potentiating effect on the sensitivity of CSLVA fibers to adenosine injection or lung inflation was completely blocked by pretreatment with capsazepine (a TRPV1 receptor antagonist) but was unaffected by pretreatment with AM281 (a CB1 receptor antagonist). In spontaneously breathing rats, right atrial injection of adenosine evoked an apneic response that is presumably mediated through CSLVA fibers. Similarly, the adenosine-evoked apneic response was potentiated during AEA infusion, and this potentiating effect was also completely prevented by pretreatment with capsazepine. These results suggest that AEA infusion at the dose tested produces a mild activation of TRPV1 receptors and this nonspecifically increases CSLVA fiber sensitivity to chemical and mechanical stimulation.

capsaicin-sensitive lung vagal afferent fibers; afferent sensitization