(964.2) Neurokinin 1 and 2 Receptors Differently Modulate PEG2- and Citric Acid-Induced Cough and Ventilatory Responses

Poster Board Number: E654

Jianguo Zhuang (Lovelace Biomedical Research Institute), Xiuping Gao (Lovelace Biomedical Research Institute), Lei Zhao (Lovelace Biomedical Research Institute), Wan Wei (Lovelace Biomedical Research Institute), Fadi Xu (Lovelace Biomedical Research Institute)

Inhalation of aerosolized citric acid (CA) or prostaglandin E2 (PGE2) provokes distinct cough patterns (Type I vs. II) and ventilatory responses (substantial hyperventilation vs. slight tachypnea) in humans and guinea pigs. Substance P (SP) and neurokinin A (NKA) are peripherally released mainly by vagal sensory fibers and capable of affecting CA-induced cough and ventilatory response via preferentially activating neurokinin 1 and 2 receptors (NK1R and NK2R) respectively. The goal of this study was to determine the impacts of CA and PGE2 exposure on pulmonary SP and NKA levels and the roles of NK1R and NK2R in CA- and PGE2-evoked cough and ventilatory responses. In unanesthetized guinea pigs, we determined: (1) pulmonary SP and NKA contents after CA or PGE2 exposure for 10 min; (2) effects of vehicle, CP-99994 and SR-48968 (a NK1R and a NK2R antagonist) given by intraperitoneal injection (IP) or aerosol inhalation (IH) on CA- and PGE2-evoked cough and ventilation; and (3) immunoreactive expression of NK1R/NK2R in vagal sensory neurons labeled by TRPV1 (responsible for Type I cough) or EP3 receptors (responsible for Type II cough). CA and PGE2 exposure evoked Type I and II cough respectively associated with different degree of increases in pulmonary SP and NKA. CP-99994 and SR-48968 via both IP and IH similarly depressed the cough responses to CA with less impact on the cough response to PGE2 exposure and substantially inhibited or blocked the evoked ventilatory responses to both CA and PGE2. Moreover, NK1R and NK2R co-expressed in vagal C-neurons labeled by TRPV1 or EP3 receptors. These results suggest that the endogenously released SP and NKA play an important role in generating the cough and ventilatory responses to CA and maintaining the ventilatory response to PGE2, at least in part, via activation of vagal C-neurons expressing NK1R and NK2R. 

Support or Funding Information

TRPV1, EP3, substance P, neurokinin A, hyperventilation, tachypnea

TRPV1, EPlt;subgt;3lt;/subgt;, substance P, neurokinin A, hyperventilation, tachypneaamp;nbsp; amp;nbsp;lt;brgt;