title: Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response.
abstract: Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA1 receptor, ADA1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA1R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin.
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Zang
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA; Department of Physiology, University of Kentucky, Lexington, KY, USA. Electronic address: fxu@lrri.org.
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000097:blood / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013373:Substance P; D009538:Nicotine; D000241:Adenosine; D002211:Capsaicin
keywords: Adenosine; NK1R; Nodose/jugular ganglion; SIDS; TRPV1; nAChRs