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Neurokinin 1 and 2 Receptors Differently Modulate PEG 2 ‐ and Citric Acid‐Induced Cough and Ventilatory Responses
Author(s) -
Zhuang Jianguo,
Gao Xiuping,
Zhao Lei,
Wei Wan,
Xu Fadi
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.l7759
Subject(s) - neurokinin a , substance p , cough reflex , inhalation , hyperventilation , chemistry , endocrinology , medicine , tachykinin receptor , anesthesia , receptor , reflex , neuropeptide
Inhalation of aerosolized citric acid (CA) or prostaglandin E 2 (PGE 2 ) 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 (NK 1 R and NK 2 R) respectively. The goal of this study was to determine the impacts of CA and PGE 2 exposure on pulmonary SP and NKA levels and the roles of NK 1 R and NK 2 R in CA‐ and PGE 2 ‐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 NK 1 R and a NK 2 R antagonist) given by intraperitoneal injection (IP) or aerosol inhalation (IH) on CA‐ and PGE 2 ‐evoked cough and ventilation; and (3) immunoreactive expression of NK 1 R/NK 2 R in vagal sensory neurons labeled by TRPV1 (responsible for Type I cough) or EP 3 receptors (responsible for Type II cough). CA and PGE 2 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 PGE 2 exposure and substantially inhibited or blocked the evoked ventilatory responses to both CA and PGE 2 . Moreover, NK 1 R and NK 2 R co‐expressed in vagal C‐neurons labeled by TRPV1 or EP 3 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 PGE 2 , at least in part, via activation of vagal C‐neurons expressing NK 1 R and NK 2 R.