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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/L1104    most recent 00163.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 Gu, Q. Articles by Lee, L.-Y. Search for Related Content PubMed PubMed Citation Articles by Gu, Q. Articles by Lee, L.-Y.

Sensitization of pulmonary chemosensitive neurons by bombesin-like peptides in rats

Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky

Submitted 12 April 2005 ; accepted in final form 15 July 2005

Small cell lung cancer (SCLC) patients suffer from pulmonary stresses such as dyspnea and chest pain, and the pathogenic mechanisms are not known. SCLC cells secrete a variety of bioactive neuropeptides, including bombesin-like peptides. We hypothesize that these peptides may enhance the sensitivity of the pulmonary chemosensitive nerve endings, contributing to the development of these pulmonary stresses in SCLC patients. This study was therefore carried out to determine the effects of bombesin and gastrin-releasing peptide (GRP), a major bombesin-like peptide, on the sensitivities of pulmonary chemoreflex and isolated pulmonary vagal chemosensitive neurons. In anesthetized, spontaneously breathing rats, intravenous infusion of bombesin or GRP significantly amplified the pulmonary chemoreflex responses to chemical stimulants such as capsaicin and ATP. The enhanced responses were completely abolished by perineural capsaicin treatment of both cervical vagi, suggesting the involvement of pulmonary C-fiber afferents. In isolated pulmonary vagal chemosensitive neurons, pretreatment with bombesin or GRP potentiated the capsaicin-induced Ca²⁺ transient. This sensitizing effect was further demonstrated in patch-clamp recording studies; the sensitivities of these neurons to both chemical (capsaicin and ATP) and electrical stimuli were significantly enhanced by the presence of either bombesin or GRP. In summary, our results have demonstrated that bombesin and GRP upregulate the pulmonary chemoreflex sensitivity in vivo and the excitability of isolated pulmonary chemosensitive neurons in vitro.

gastrin-releasing peptide; pulmonary stress; small cell lung cancer; vagal sensory neuron